Biomechanical analysis of different back-supporting exoskeletons regarding musculoskeletal loading during lifting and holding.

Industrial back support exoskeletons (BSEs) are a promising approach to addressing low back pain (LBP) which still affect a significant proportion of the workforce. They aim to reduce lumbar loading, the main biomechanical risk factor for LBP, by providing external support to the lumbar spine. The aim of this study was to determine the supporting effect of one active (A1) and two passive (P1 and P2) BSEs during different manual material handling tasks. Kinematic data and back muscle activity were collected from 12 subjects during dynamic lifting and static holding of 10 kg. Mean and peak L5/S1 extension moments, L5/S1 compression forces and muscle activation were included in the analysis. During dynamic lifting all BSEs reduced peak (12-26 %) and mean (4-17 %) extension moments and peak (10-22 %) and mean (4-15 %) compression forces in the lumbar spine. The peak (13-28 %) and mean (4-32 %) activity of the back extensor muscles was reduced accordingly. In the static holding task, analogous mean reductions for P1 and P2 of L5/S1 extension moments (12-20 %), compression forces (13-23 %) and muscular activity (16-23 %) were found. A1 showed a greater reduction during static holding for extension moments (46 %), compression forces (41 %) and muscular activity (54 %). This pronounced difference in the performance of the BSEs between tasks was attributed to the actuators used by the different BSEs.

Variability in Perioperative Steroid Therapy Regimen for Cochlear Implantation as It Relates to Hearing Preservation.

HYPOTHESIS: We aimed to identify practice trends and association between physician training and administration of perioperative steroids for cochlear implantation (CI) as it relates to hearing preservation. BACKGROUND: Perioperative steroid therapy regimens are postulated to protect residual hearing and improve hearing preservation outcomes in CI. METHODS: A 27-question online survey was developed by the senior authors using the Qualtrics Survey Tool, then distributed via email from September to November 2022 to otolaryngologists specializing in otology or neurotology and who practice in the United States or Canada. RESULTS: The survey was sent to 463 physicians, 162 (35.0%) of whom completed the survey. One hundred forty-four (31.1%) responses underwent analysis. All physicians administering preoperative steroids (n = 31) prefer preoperative oral prednisone. Of 143 physicians administering intraoperative steroids, 54.5% prefer intraoperative intravenous dexamethasone. More than half (77.6%) of 85 physicians administering postoperative steroids prefer postoperative oral prednisone. Postoperative steroid administration (p < 0.006) and taper utilization (p < 0.041) were greater among physicians who complete greater than 40 CIs annually (n = 47 [71.2%]; n = 30 [49.2%]) than physicians who complete up to 40 CIs annually (n = 37 [48.7%]; n = 20 [31.3%]), respectively. Physicians practicing for 5 to 20 years after residency are more prevalent in using postoperative steroid tapers than physicians practicing for fewer than 5 years after and more than 20 years after residency (n = 37 [51.4%] versus n = 14 [25.5%], p < 0.001). CONCLUSION: Consensus is needed about the optimal steroid treatment for CI patients. LEVEL OF EVIDENCE: 4.

Emerging Mechanisms in the Pathogenesis of Menière's Disease: Evidence for the Involvement of Ion Homeostatic or Blood-Labyrinthine Barrier Dysfunction in Human Temporal Bones.

HYPOTHESIS: Analysis of human temporal bone specimens of patients with Menière's disease (MD) may demonstrate altered expression of gene products related to barrier formation and ionic homeostasis within cochlear structures compared with control specimens. BACKGROUND: MD represents a challenging otologic disorder for investigation. Despite attempts to define the pathogenesis of MD, there remain many gaps in our understanding, including differences in protein expression within the inner ear. Understanding these changes may facilitate the identification of more targeted therapies for MD. METHODS: Human temporal bones from patients with MD (n = 8) and age-matched control patients (n = 8) were processed with immunohistochemistry stains to detect known protein expression related to ionic homeostasis and barrier function in the cochlea, including CLDN11, CLU, KCNJ10, and SLC12A2. Immunofluorescence intensity analysis was performed to quantify protein expression in the stria vascularis, organ of Corti, and spiral ganglion neuron (SGN). RESULTS: Expression of KCNJ10 was significantly reduced in all cochlear regions, including the stria vascularis (9.23 vs 17.52, p = 0.011), OC (14.93 vs 29.16, p = 0.014), and SGN (7.69 vs 18.85, p = 0.0048) in human temporal bone specimens from patients with MD compared with control, respectively. CLDN11 (7.40 vs 10.88, p = 0.049) and CLU (7.80 vs 17.51, p = 0.0051) expression was significantly reduced in the SGN. CONCLUSION: The results of this study support that there may be differences in the expression of proteins related to ionic homeostasis and barrier function within the cochlea, potentially supporting the role of targeted therapies to treat MD.

Dissection of Adult Mouse Stria Vascularis for Single-Nucleus Sequencing or Immunostaining.

Endocochlear potential, which is generated by the stria vascularis, is essential to maintain an environment conducive to appropriate hair cell mechanotransduction and ultimately hearing. Pathologies of the stria vascularis can result in a decreased hearing. Dissection of the adult stria vascularis allows for focused single-nucleus capture and subsequent single-nucleus sequencing and immunostaining. These techniques are used to study stria vascularis pathophysiology at the single-cell level. Single-nucleus sequencing can be used in the setting of transcriptional analysis of the stria vascularis. Meanwhile, immunostaining continues to be useful in identifying specific populations of cells. Both methods require proper stria vascularis dissection as a prerequisite, which can prove to be technically challenging.

The role of the stria vascularis in neglected otologic disease.

The stria vascularis (SV) has been shown to play a critical role in the pathogenesis of many diseases associated with sensorineural hearing loss (SNHL), including age-related hearing loss (ARHL), noise-induced hearing loss (NIHL), hereditary hearing loss (HHL), and drug-induced hearing loss (DIHL), among others. There are a number of other disorders of hearing loss that may be relatively neglected due to being underrecognized, poorly understood, lacking robust diagnostic criteria or effective treatments. A few examples of these diseases include autoimmune inner ear disease (AIED) and/or autoinflammatory inner ear disease (AID), Meniere's disease (MD), sudden sensorineural hearing loss (SSNHL), and cytomegalovirus (CMV)-related hearing loss (CRHL). Although these diseases may often differ in etiology, there have been recent studies that support the involvement of the SV in the pathogenesis of many of these disorders. We strive to highlight a few prominent examples of these frequently neglected otologic diseases and illustrate the relevance of understanding SV composition, structure and function with regards to these disease processes. In this study, we review the physiology of the SV, lay out the importance of these neglected otologic diseases, highlight the current literature regarding the role of the SV in these disorders, and discuss the current strategies, both approved and investigational, for management of these disorders.

Retained tracheostomy stay suture with migration into the glottic airway: A case report.

The stay-suture technique (SST) helps ensure safe replacement of the tracheostomy tube after accidental decannulation. We describe a patient found to have a retained stay suture in the glottis 2 weeks post-decannulation. It is important to appreciate the possible complications associated with SST, including airway compromise, infection, and laryngospasm.

Poly (acetyl, arginyl) glucosamine disrupts Pseudomonas aeruginosa biofilms and enhances bacterial clearance in a rat lung infection model.

Pseudomonas aeruginosa is a common opportunistic pathogen that can cause chronic infections in multiple disease states, including respiratory infections in patients with cystic fibrosis (CF) and non-CF bronchiectasis. Like many opportunists, P. aeruginosa forms multicellular biofilm communities that are widely thought to be an important determinant of bacterial persistence and resistance to antimicrobials and host immune effectors during chronic/recurrent infections. Poly (acetyl, arginyl) glucosamine (PAAG) is a glycopolymer that has antimicrobial activity against a broad range of bacterial species, and also has mucolytic activity, which can normalize the rheological properties of cystic fibrosis mucus. In this study, we sought to evaluate the effect of PAAG on P. aeruginosa bacteria within biofilms in vitro, and in the context of experimental pulmonary infection in a rodent infection model. PAAG treatment caused significant bactericidal activity against P. aeruginosa biofilms, and a reduction in the total biomass of preformed P. aeruginosa biofilms on abiotic surfaces, as well as on the surface of immortalized cystic fibrosis human bronchial epithelial cells. Studies of membrane integrity indicated that PAAG causes changes to P. aeruginosa cell morphology and dysregulates membrane polarity. PAAG treatment reduced infection and consequent tissue inflammation in experimental P. aeruginosa rat infections. Based on these findings we conclude that PAAG represents a novel means to combat P. aeruginosa infection, and may warrant further evaluation as a therapeutic.

Utilizing Single Cell RNA-Sequencing to Implicate Cell Types and Therapeutic Targets for SSNHL in the Adult Cochlea.

OBJECTIVE: To identify genes implicated in sudden sensorineural hearing loss (SSNHL) and localize their expression in the cochlea to further explore potential pathogenic mechanisms and therapeutic targets. STUDY DESIGN: Systematic literature review and bioinformatics analysis. DATA SOURCES: The following sources were searched from inception through July 2, 2020: PubMed-NCBI, MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, OpenGrey, GreyNet, GreyLiterature Report, and European Union Clinical Trials Registry. PubMed-NCBI and MEDLINE were additionally searched for human temporal bone histopathologic studies related to SSNHL. METHODS: Literature review of candidate SSNHL genes was conducted according to PRISMA guidelines. Existing temporal bone studies from SSNHL patients were analyzed to identify the most commonly affected inner ear structures. Previously published single-cell and single-nucleus RNA-Seq datasets of the adult mouse stria vascularis, as well as postnatal day 7 and 15 mouse cochlear hair cells and supporting cells, were utilized for localization of the SSNHL-related genes curated through literature review. CONCLUSIONS: We report 92 unique single nucleotide polymorphisms (SNPs) in 76 different genes that have been investigated in relation to SSNHL in the literature. We demonstrate that a subset of these genes are expressed by cell types in the adult mouse stria vascularis and organ of Corti, consistent with findings from temporal bone studies in human subjects with SSNHL. We highlight several potential genetic targets relevant to current and possible future SSNHL treatments.

Hearing restoration and the stria vascularis: evidence for the role of the immune system in hearing restoration.

PURPOSE OF REVIEW: This article reviews the current literature regarding the pathogenesis of immune-mediated sensorineural hearing loss, utilizes previously published single-nucleus transcriptional profiles to characterize cytokine and cytokine receptor expression in the adult stria vascularis cell types to support immune system interaction with the stria vascularis and reviews the current literature on immunomodulatory agents currently being used for hearing-restoration treatment. RECENT FINDINGS: The literature review highlights recent studies that elucidate many cytokines and immune markers, which have been linked to various immune-mediated disease processes that have been observed with sensorineural hearing loss within the stria vascularis and highlights recent publications studying therapeutic targets for these pathways. SUMMARY: This review highlights the current literature regarding the pathogenesis of immune-mediated hearing loss. The role of cochlear structures in human temporal bones from patients with immune-mediated sensorineural hearing loss are highlighted, and we review cytokine signalling pathways relevant to immune-mediated sensorineural hearing loss and localize genes encoding both cytokine and cytokine receptors involved in these pathways. Finally, we review immunomodulatory therapeutics in light of these findings and point to opportunities for the application of novel therapeutics by targeting these signalling pathways.

The significance of low first trimester serum progesterone in ongoing early pregnancies presenting as pregnancies of unknown location.

OBJECTIVES: The primary objective of this study was to ascertain whether there is association between low initial serum progesterone, sonographic parameters and clinical outcomes in women presenting with pregnancies of unknown location (PUL), which are found to be ongoing at their follow up scans in the first trimester. STUDY DESIGN: This was a non-interventional retrospective cohort study of 1056 patients spanning a 14-year period, conducted in the Early Pregnancy Unit (EPU) of an inner-city teaching hospital. Patients who had an ongoing singleton first trimester pregnancy after presenting with PUL were identified and categorised as having low progesterone if it was 32 nmol/l or lower. The crown-rump length (CRL), mean gestational sac diameter (MGSD) and gestational sac volume (GSV) were measured when the embryo was first seen, and the pregnancy outcome recorded. RESULTS: Pregnancies with low progesterone tended to have smaller gestational sacs (GS) on follow up scan (p = 0.001) and the sac was smaller than expected for a given CRL (p = 0.000). There was no ultrasound parameter that was characteristic of low progesterone. The observation of a smaller than expected MGSD for a given CRL remained even when only pregnancies with normal outcomes were analysed. Clinical outcome data were available for 854 (80.9 %) women. Overall, 81.4 % (n = 34/43) of pregnancies with low progesterone resulted in livebirth, compared to 91.7 % (n = 744/811) livebirths in pregnancies with higher levels (p = 0.0454). CONCLUSION: Pregnancies with low progesterone tend to have a smaller GS compared to those with a higher progesterone, and the GSs are smaller than expected for a given CRL. The current study shows that women with low progesterone at the start of pregnancy remain at higher risk of miscarriage, even when the pregnancy is initially found to be viable in the first trimester. These pregnancies also tend to be associated with the sonographic finding of a smaller GS than expected for a given gestational age, regardless of eventual outcome.

In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea.

BACKGROUND: Treatment of many types of hearing instability in humans, including sudden sensorineural hearing loss, Meniere's disease, and autoimmune inner ear disease, rely heavily on the utilization of corticosteroids delivered both by oral and transtympanic routes. Despite this use, there is heterogeneity in the response to treatment with corticosteroids in humans with these diseases. The mechanisms by which corticosteroids exert their effect and the cell types in which they exert their effects in the inner ear remain poorly characterized. In this study, we localize steroid-responsive genes to cochlear cell types using previously published transcriptome datasets from the mammalian cochlea. METHODS: Steroid-responsive genes were localized to specific cochlear cell types using existing transcriptome datasets from wild-type mammalian cochlea exposed to systemic and transtympanic steroids, as well as previously published single-cell and single-nucleus RNA-sequencing datasets from the mammalian cochlea. Gene ontology (GO) analysis of differentially expressed genes (DEGs) was performed using PANTHER to investigate cellular processes implicated in transtympanic vs. systemic steroid action in the cochlea. RESULTS: Steroid-responsive genes were localized to specific cell types and regions in the cochlea including the stria vascularis, organ of Corti, and spiral ganglion neurons (SGN). Analyses demonstrate differential prevalence of steroid-responsive genes. GO analysis demonstrated steroid-responsive DEGs in the SGN to be associated with angiogenesis, apoptosis, and cytokine-mediated anti-inflammatory pathways. CONCLUSIONS: Single-cell and single-nucleus transcriptome datasets localize steroid-responsive genes to specific regions in the cochlea. Further study of these regionally-specific steroid-responsive genes may provide insight into the mechanisms of and clinical response to corticosteroids in diseases of hearing instability.

Hip fractures in centenarians: a multicentre review of outcomes.

INTRODUCTION: Advances in healthcare have resulted in an increasing UK population, with the proportion of elderly individuals expanding significantly, including centenarians. Hospitals can expect to see growing numbers of so-called 'super-elderly' patients with trauma, a majority of whom will have hip fractures. We performed a multicentre review of hip fracture outcomes in centenarians to assess whether being an outlier in age correlates with poorer prognosis. METHODS: Centenarians admitted to Basingstoke, Southampton, Dorset, and Salisbury district hospitals with hip fractures between January 2014 and June 2019 were included. Electronic records were searched to obtain demographics, functional status, and admission details. RESULTS: A total of 60 centenarians were included, with a median age of 101 years (range 100-108 years), 85% of whom were female; 29 were admitted from their own home or sheltered housing and 31 from nursing or residential care; 33 had some outdoor mobility, 26 only mobilised indoors, and 1 had no mobility. Common comorbidities were renal and heart disease and dementia. Of the total, 56 underwent surgery, 51 within 36 hours. In terms of accommodation, 63.4% returned to their pre-injury level of independence. At 30 days, three months, and one year, mortality rates were 27% (n = 16), 40% (n = 24) and 55% (n = 33), respectively. CONCLUSION: Trauma in the elderly population is an area of growing interest, yet few studies address centenarians with hip fractures. This work demonstrates that mortality rates within one year of injury were high, but almost half survived beyond a year. Two-thirds of patients regained their pre-injury level of independence, suggesting that functional recovery may not be as poor as previously reported.

Cochlear Implantation and Perioperative Management in Autoimmune Inner Ear Disease: A Systematic Review and Meta-Analysis.

Objective: To assess outcomes in autoimmune inner ear disease (AIED) after cochlear implantation (CI) through systematic review and meta-analysis. Databases Reviewed: PubMed, MedLine, Embase, and CINAHL. Methods: Databases were queried for inclusion of AIED patients who underwent CI with outcomes recorded ≥3 months postoperatively. We examined demographics, pure-tone average (PTA), speech perception, preoperative imaging, intraoperative management, and postoperative complications. Results: Twenty-six articles encompassing 124 patients met inclusion criteria. Mean implantation age was 26.2 years (range 4-65 years) with average length of follow-up at 28.2 months (range 3-120 months). Meta-analysis demonstrated significant improvement in speech perception following CI. There was a statistically significant improvement in speech recognition score (SRS) (standard mean difference [SMD] = 6.5, 95% confidence interval [CI], 4.8-8.0, P < 0.0001) as well as word recognition score (WRS) (SMD = 5.5, 95% CI, 4.2-6.8, P < 0.0001) after CI. Anomalous preoperative radiologic manifestations were reported by 57.7% (15/26) studies. Disease activity-related intraoperative adjustment was noted in 57.7% (15/26) studies; common consequences were cochlear drill-out (53.3%), difficult round window insertion (26.7%), and scala vestibuli insertion (26.7%). Frequent postoperative complications noted in 26.9% (7/26) studies included systemic AIED flares (71.4%) and wound healing delay (42.9%). Conclusion: Findings of this systematic review of AIED cochlear implant literature demonstrate a lack of consistent reporting standards for PTA and speech perception as well as a lack of long-term follow-up. Despite these findings, meta-analysis suggests that CI is a viable treatment for improving speech perception in AIED patients.

Novel Therapy of Bicarbonate, Glutathione, and Ascorbic Acid Improves Cystic Fibrosis Mucus Transport.

Defective airway mucus clearance is a defining characteristic of cystic fibrosis lung disease, and improvements to current mucolytic strategies are needed. Novel approaches targeting a range of contributing mechanisms are in various stages of preclinical and clinical development. ARINA-1 is a new nebulized product comprised of ascorbic acid, glutathione, and bicarbonate. Using microoptical coherence tomography, we tested the effect of ARINA-1 on central features of mucociliary clearance in F508del/F508del primary human bronchial epithelial cells to assess its potential as a mucoactive therapy in cystic fibrosis. We found that ARINA-1 significantly augmented mucociliary transport rates, both alone and with CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy, whereas airway hydration and ciliary beating were largely unchanged compared with PBS vehicle control. Analysis of mucus reflectivity and particle-tracking microrheology indicated that ARINA-1 restores mucus clearance by principally reducing mucus layer viscosity. The combination of bicarbonate and glutathione elicited increases in mucociliary transport rate comparable to those seen with ARINA-1, indicating the importance of this interaction to the impact of ARINA-1 on mucus transport; this effect was not recapitulated with bicarbonate alone or bicarbonate combined with ascorbic acid. Assessment of CFTR chloride transport revealed an increase in CFTR-mediated chloride secretion in response to ARINA-1 in CFBE41o- cells expressing wild-type CFTR, driven by CFTR activity stimulation by ascorbate. This response was absent in CFBE41o- F508del cells treated with VX-809 and primary human bronchial epithelial cells, implicating CFTR-independent mechanisms for the effect of ARINA-1 on cystic fibrosis mucus. Together, these studies indicate that ARINA-1 is a novel potential therapy for the treatment of impaired mucus clearance in cystic fibrosis.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

The effect of CFTR modulators on a cystic fibrosis patient presenting with recurrent pancreatitis in the absence of respiratory symptoms: a case report.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder of the epithelial CFTR apical chloride channel resulting in multi-organ manifestations, including pancreatic exocrine secretion. In the pancreas, CFTR abnormality results in abnormally viscous secretions that obstruct proximal ducts leading to fibrotic injury and ultimately pancreatic insufficiency in 85% of the CF population. CFTR modulators, including the potentiator ivacaftor, augment channel gating to restore 30-50% of CFTR-mediated anion transport. While CFTR modulation has been shown to alkalinize the pH of the alimentary tract and potentially augment pancreatic enzyme activity, the effect of ivacaftor on recurrent pancreatitis is emerging. Here we describe a case of a patient with CF (R117H/7 T/F508del) who presented with recurrent pancreatitis who was effectively treated with ivacaftor in the absence of respiratory symptoms. CASE PRESENTATION: A 24-year-old white male with past medical history of recurrent acute pancreatitis presented for evaluation following a referral from an outside hospital. The patient reported a lifetime of gastrointestinal symptoms requiring over 20 hospitalizations for pancreatitis in the last 10 years. Prior U/S and CT imaging for pancreatitis ruled out gallstones or anatomical etiologies. Family history included a brother with CF carrier status who suffered from recurrent acute pancreatitis. Sweat chloride testing was suggestive of CFTR dysfunction (57 mmol/L). Genetic testing demonstrated disease causing CFTR mutations: R1117H/7 T/F508del. Patient was prescribed pancrelipase, however, he reported worsened gas and diarrhea symptoms. Pancrelipase was discontinued and the patient was prescribed ivacaftor 150 mg BID. After 6 weeks of ivacaftor treatment, patient reported improved gastrointestinal symptoms. For an additional 19 months, patient reported no episodes of pancreatitis until he discontinued ivacaftor. Over the next 3 weeks, patient experienced progressive nausea and sharp epigastric pain and laboratory studies confirmed pancreatitis. Patient was subsequently lost to follow up. CONCLUSIONS: These findings support a possible relationship between the use of CFTR modulators, such as ivacaftor, in the management of recurrent pancreatitis in the setting of patients with cystic fibrosis and a CFTR mutation with residual CFTR activity or otherwise known to be responsive in vitro. Ivacaftor may be useful for recurrent pancreatitis, even in the absence of respiratory morbidity.

Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency.

PURPOSE: Pyruvate kinase deficiency (PKD) is a rare disease and understanding of its epidemiology and associated burden remains limited. With no current curative therapy, clinical manifestations can be life threatening, clinically managed by maintaining adequate hemoglobin levels through transfusion and subsequent support, but with frequent complications. Treatment goals are to maintain/improve the patient's quality of life. With new therapies, reliable, valid, and relevant patient-reported outcome (PRO) tools are required for use in clinical trials. METHODS: Systematic literature search identified no current PRO tools for capturing/measuring the impact of PKD and treatments in clinical trials. Therefore, the search strategy was revised to consider conditions analogous to PKD in terms of symptoms and impacts that might serve as parallels to the experience in PKD; this included sickle cell anemia, thalassemia, and hemolytic anemia. Psychometric properties, strengths, and weakness of selected appropriate PRO instruments were compared, and recommendations made for choice of PRO tools. RESULTS: In adult populations, EORTC QLQ C30 and SF-36v2 are recommended, the former being a basic minimum, covering generic HRQoL, and core symptoms such as fatigue. In pediatric populations, PedsQL Generic Core Scale to measure HRQoL and PedsQL MFS scale to measure fatigue are recommended. CONCLUSIONS: Some symptoms/life impacts may be unique to PKD and not observable in analogous conditions. A 'Physico-Psychosocial Model' derived from the 'Medical Model' is proposed to form the basis for a hypothesized conceptual framework to address the development of PKD-specific PRO instruments.

Natural history of early first-trimester pregnancies implanted in Cesarean scars.

OBJECTIVE: To describe the ultrasound findings and natural history of pregnancies implanted within or on Cesarean section scars in the first trimester of pregnancy. METHODS: This was a prospective observational study of 10 women diagnosed with a pregnancy implanted in or on a Cesarean section scar in the first trimester, who declined medical intervention because of their desire to continue the pregnancy. The study population comprised women at < 12 weeks' gestation who were seen in our early pregnancy unit between January 2011 and September 2013. Nine women were followed up by serial ultrasound examinations and had detailed care plans for delivery at King's College Hospital (KCH). One woman was followed up and delivered at another teaching hospital. The first-trimester ultrasound findings were compared with the clinical outcome of the pregnancy. RESULTS: The nine patients who were followed up at KCH developed ultrasound findings of morbidly adherent placenta (MAP) in the second and third trimesters. All 10 patients were diagnosed with MAP at the time of delivery by Cesarean section. The gestational age at delivery ranged from 26 to 38 weeks. The uterus was conserved in five patients, and Cesarean hysterectomy was performed in the remaining five. All three women with complete implantation of the gestational sac within the scar and two of three cases with placental lakes in the first trimester had hysterectomies. The two cases with bulging of the gestational sac out of the uterine contour had a preterm emergency hysterectomy due to placenta percreta. Histology confirmed placenta accreta in the five hysterectomy specimens. There were no fetal or neonatal complications. CONCLUSIONS: Implantation of a pregnancy on or in a Cesarean section scar is a precursor of MAP; however, the degree of morbidity associated with this implantation is variable and difficult to predict based on first-trimester ultrasound findings only. The assessment of ongoing pregnancies implanted in Cesarean scars is most beneficial when performed between 7 and 9 weeks' gestation. Complete implantation within the myometrial defect, bulging of the trophoblast from the uterine contour and large placental lakes in the first trimester are ultrasound findings that may predict severe placenta accreta or percreta and consequently a poor outcome.

Early postpartum pup preference is altered by gestational cocaine treatment: associations with infant cues and oxytocin expression in the MPOA.

Cross-fostering studies suggest cocaine-induced deficits in maternal behavior could be associated with altered behavior of offspring following prenatal cocaine-exposure. Neonatal vocalizations are an important offspring cue facilitating early interactions between dam and rodent pup offspring and have been shown to be altered following prenatal cocaine-exposure. It is unclear how variations in acoustic parameters of USVs impact maternal behavior and the mechanism(s) underlying these processes. The present study examined differences in cocaine-exposed and control rodent dam maternal preference of cocaine-exposed or untreated pups in a dual choice apparatus. Relationship of preference-like behavior with pup USVs and dam oxytocin expression was explored. Gestational cocaine-exposure interfered with preference-like behavior of dams on postpartum day 1 with cocaine-exposure associated with decreased time spent on the cocaine-exposed pup side compared to the control pup side, and decreases in preference-like behavior associated in part with decreased number of USVs being emitted by cocaine-exposed pups. On postpartum day 5, decreased oxytocin expression in the medial preoptic area was associated with altered preference-like behavior in cocaine-exposed dams, including frequency and latency to touch/sniff pups. Results indicate cocaine's effects on the mother-infant relationship is likely synergistic, in that cocaine influences mother and offspring both independently and concertedly and that variations within pup vocalizations and the oxytocin system may be potential mechanism(s) underlying this synergistic relationship during the postpartum period.

The psychological effects and patient acceptability of a test to predict viability in early pregnancy: a prospective randomised study.

OBJECTIVE: To establish if women obtain any measurable short term psychological benefit or perceived benefit from having a test to determine the probability of their pregnancy being on-going when this is uncertain on ultrasound examination. STUDY DESIGN: This was a prospective randomised controlled study conducted January 2012-June 2012 at the EPU of King's College Hospital. The study population was women who conceived spontaneously and had a single intrauterine gestational sac of <20mm mean diameter, with no visible embryo on their first ultrasound scan. Eligible women were randomised to have a test to calculate the probability of viability (cases) or not (controls). Depression and anxiety levels were calculated using the Hospital Anxiety and Depression Score (HADS) and were performed prior to randomisation and seven days later. A repeat scan for pregnancy outcome was performed after one to two weeks as clinically indicated. A sample size of 69 in each group was calculated to have 80% power to detect a probability of 0.362 that an observation in the cases was less than an observation in controls using a Wilcoxon Mann-Whitney rank-sum test with a 0.05 two-sided significance. RESULTS: At recruitment there was no significant difference in anxiety levels between cases and controls. After seven days anxiety levels were significantly lower in cases than controls (p=0.04). Of those who received the probability score, 55/70 (78.6% 95% CI 67.5-86.7%) found it useful and 58/70 (82.9% 95% CI 72.2-90.1) would choose to have the test in a future pregnancy if indicated. CONCLUSIONS: This study has demonstrated that there is evidence of psychological benefit from a simple blood test that gives women the likelihood that their pregnancy will be on-going at the next scan.