Pediatric postmortem CT angiography: validation of vascular access for PMCT angiography in stillbirths, babies and toddlers.

PURPOSE: The use of angiography in postmortem CT angiography (PMCTA) has several advantages. In adults, femoral vascular access is well established. Due to the small and specific anatomy in fetuses and infants, the technique has to be adapted, especially regarding the vascular access. The aim of this study was to evaluate vascular access for pediatric PMCTA (pedPMCTA). MATERIALS AND METHODS: Ten pedPMCTAs were performed in stillbirths, babies, and one toddler. A femoral approach by cannulation of the femoral artery and vein, an umbilical approach by cannulation of the umbilical vessels, and an intraosseous approach by an intraosseous needle were evaluated by handling and resulting imaging. RESULTS: The insertion of a cannula with a size of 18-20 G in the femoral vessels was possible in babies. An umbilical access with peripheral venous cannulas with a size of 14-20 G was feasible in stillbirths and newborns. An intraosseous access is advisable as equal alternative to umbilical and in cases where a femoral access is not possible. The most significant problem with the vascular access is the extravasation of contrast media, but this can be reduced significantly with practice. CONCLUSION: When performing pedPMCTA, an umbilical vascular access is recommended if an umbilical cord with open vessels is still present. Otherwise, a bone marrow access should be preferred in the presence of an arteriovenous shunt or if only the venous system needs to be shown. If that is not the case, the femoral access with the possibility to separate venous and arterial scan should be used.

COVID-19 and vertical transmission: assessing the expression of ACE2/TMPRSS2 in the human fetus and placenta to assess the risk of SARS-CoV-2 infection.

BACKGROUND: Pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, but little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. METHODS: We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT-qPCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. FINDINGS: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co-express the two proteins across the second trimester or at term. INTERPRETATION: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. TWEETABLE ABSTRACT: This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS-CoV-2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.

Missed opportunities for ovarian salvage in children: an 8-year review of surgically managed ovarian lesions at a tertiary pediatric surgery centre.

INTRODUCTION: The aetiology and management of ovarian pathology in children differs between antenatal and postnatal lesions. However, all lesions may present acutely due to adnexal torsion. In this setting, opportunities to preserve fertility with ovary-sparing surgery (OSS) may be missed. Some studies suggest that pediatric and adolescent gynaecology (PAG) input in care is associated with OSS. METHODS: A retrospective cohort study of children undergoing surgery for ovarian pathology at a tertiary pediatric surgery centre over an 8-year period (2011-2018). Patient factors, lesion characteristics and PAG involvement were examined for association with OSS using multivariate logistic regression. RESULTS: Thirty-five patients with ovarian pathology managed surgically were included. Ten were infants with lesions detected antenatally; all were managed by pediatric surgeons (PS) alone at median age 2 weeks (1 day-25 weeks). Twenty-five patients presented postnatally at median age 11 (0.75-15) years. In total, there were 16 cases of adnexal torsion, each managed primarily by PS. Twelve underwent oophorectomy and six (50%) of these cases had viable ovarian tissue on histology. Furthermore, two infants with large simple cysts were similarly managed by unnecessary oophorectomy based on histology. Overall rate of OSS was 46% and PAG involvement was the only factor associated with ovarian salvage. CONCLUSION: Differences in surgical management between PAGs and PS may be attributable to the different patient populations they serve. We recommend improving the knowledge of PS trainees in OSS approaches for adnexal torsion and large benign lesions.

Improvise, Adapt, Overcome: mobile phone LED used as a light source for cystoscopy and resection of posterior urethral valves in a low-cost setting.

We describe use of an improvised light source to perform cystoscopy and PUV resection while working in a resource poor setting. The light emitted from a mobile telephone LED (iPhone 6) was sufficient to perform the procedure and there was an excellent surgical outcome. We hope that this report may prove to be helpful to colleagues working in similar circumstances with limited resources.

Sleep disturbance in adults with cancer: a systematic review of evidence for best practices in assessment and management for clinical practice.

Sleep disturbance is prevalent in cancer with detrimental effects on health outcomes. Sleep problems are seldom identified or addressed in cancer practice. The purpose of this review was to identify the evidence base for the assessment and management of cancer-related sleep disturbance (insomnia and insomnia syndrome) for oncology practice. The search of the health literature included grey literature data sources and empirical databases from June 2004 to June 2012. The evidence was reviewed by a Canadian Sleep Expert Panel, comprised of nurses, psychologists, primary care physicians, oncologists, physicians specialized in sleep disturbances, researchers and guideline methodologists to develop clinical practice recommendations for pan-Canadian use reported in a separate paper. Three clinical practice guidelines and 12 randomized, controlled trials were identified as the main source of evidence. Additional guidelines and systematic reviews were also reviewed for evidence-based recommendations on the assessment and management of insomnia not necessarily in cancer. A need to routinely screen for sleep disturbances was identified and the randomized, controlled trial (RCT) evidence suggests benefits for cognitive behavioural therapy for improving sleep quality in cancer. Sleep disturbance is a prevalent problem in cancer that needs greater recognition in clinical practice and in future research.

Developmental changes in human dural innervation.

INTRODUCTION: There is limited published work on the abundant innervation of the human dura mater, its role and responses to injury in humans. The dura not only provides mechanical support for the brain but may also have other functions, including control of the outflow of venous blood from the brain via the dural sinuses. The trigeminal nerve supplies sensory fibres to the dura as well as the leptomeninges, intracranial blood vessels, face, nose and mouth. Its relatively large size in embryonic life suggests an importance in development; the earliest fetal reflexes, mediated by the trigeminal, are seen by 8 weeks. Trigeminal functions vital to the fetus include the coordination of sucking and swallowing and the protective oxygen-conserving reflexes. Like other parts of the nervous system, the trigeminal undergoes pruning and remodelling throughout development. METHODS: We have investigated changes in the innervation of the human dura with age in 27 individuals aged between 31 weeks of gestation and 60 years of postnatal life. Using immunocytochemistry with antibodies to neurofilament, we have found significant changes in the density of dural innervation with age RESULTS: The density of innervation increased between 31 and 40 weeks of gestation, peaking at term and decreasing in the subsequent 3 months, remaining low until the sixth decade. CONCLUSIONS: Our observations are consistent with animal studies but are, to our knowledge, the first to show age-related changes in the density of innervation in the human dura. They provide new insights into the functions of the human dura during development.

Role of injection pressure, flow and sclerosant viscosity in causing cutaneous ulceration during sclerotherapy.

The objective of the study is to evaluate the viscosity of popular sclerosants and their flow hydrodynamics through a syringe/needle to further discuss Miyake's old, venous-capillary reflux theory, using additional objective data. The following sclerosing agents were tested in the study: 75% dextrose (D75%); 50% dextrose (D50%); 5% ethanolamine oleate (Etha5%); 0.5% laureth-9 (Aet0.5%) and 0.1% sodium tetradecyl sulphate (STS0.1%). Using 5 mL syringes and 27G needles, the resulting pressures and flows for each sclerosant agent were measured. To do this, a three-way stopcock was connected between the syringe and the needle so that an arm of the stopcock could be used to measure injection pressures with a digital monitor in 1 mmHg increments. Two trials were performed: in trial 1, the syringe was attached to a Samtronic 680 infusion pump and in trial 2, the solutions were injected manually. The observed sclerosant viscosities were as follows: D75%: 0.28 Poise; D50%: 0.12 Poise; Etha5%: 0.10 Poise; Aet0.5%: 0.07 Poise; and STS0.1%: 0.04 Poise. In trial 1 (constant flow), it was observed that D75%, which had the highest viscosity of the sclerosants tested, had the highest pressure readings. In trial 2 (constant pressure), the flow obtained with the D75% solution was lower than the flow of the other solutions. In conclusion, based on the rabbit study theory, vessel size and sclerosant viscosity and strength, not extravasation, play a role in causing ulceration from injection sclerotherapy. As a result, they all affect the potential of venous-capillary reflux being caused by sclerotherapy injection and, thus, the risk of postsclerotherapeutic cutaneous ulceration.

Mast cells in the human dura: effects of age and dural bleeding.

BACKGROUND: Animal studies have shown that the dura mater contains mast cells. We investigated the density of mast cells in the human dura mater, and the changes associated with subdural haemorrhage (SDH). METHODS: Samples of the human dura were stained with tryptase antibody and were examined for mast cells. We used control cases with no dural bleeding (n = 9) and cases of fresh (n = 24) and old (n = 18) dural haemorrhage. RESULTS: Mast cells were easily found in dural samples. The mean density in controls (11.05 cells per mm(2)) was less than that in fresh SDH (15.69), which was less than that in old SDH (23.09). CONCLUSIONS: Subdural haemorrhage is associated with an increase in dural mast cell density, and the density increases as the haematoma ages. We hypothesise that dural mast cells may contribute to neurogenic inflammation and the clinical features of subdural haemorrhage.

A psychopharmacological treatment algorithm for generalised anxiety disorder (GAD).

Generalised anxiety disorder (GAD) is defined as excessive and uncontrollable worry and anxiety about everyday life situations. It is a chronic disorder, and is associated with substantial somatisation, high rates of comorbid depression and other anxiety disorders, and significant disability. The evidence base for pharmacotherapy and psychotherapy has continued to grow, and a wide range of drug choices for GAD now exists. Current guidelines for GAD generally restrict themselves to presentation of the evidence for various treatments, which, as a result, generally do not offer detailed discussion or recommendation of strategies beyond the first level of treatment, or take into account the individual circumstances of the patient. Thus, there is a lack of algorithm-based treatment guidelines for GAD. Our aim is, therefore, to present an algorithm for the psychopharmacologic management of GAD, intended for all clinicians who treat patients with GAD, where issues of pharmacotherapy are under consideration. We also hope that these GAD algorithms and other guidelines can help to identify high-priority areas that need further study. In this algorithm, we provide a sequenced approach to the pharmacotherapy of GAD, taking into account salient symptomatology and comorbidity, levels of evidence and extent of response. Special issues, including comorbidity, insomnia, suicidality, substance abuse, treatment adherence, pregnancy and lactation, cross-cultural issues, use of medication in the elderly, psychosocial treatment and dosing issues are also addressed.

Acquisition of quality gamma-ray spectra with HPGe spectrometers.

We propose practices to optimize the quality of acquired gamma-ray spectra at a radioanalytical laboratory and to assist in the identification of extraneous spectral peaks including those from limitations in the physical setup, electronics, and counting conditions. This paper offers visible comparisons of high-quality spectra with those of inferior quality. We demonstrate the impacts on gamma-ray spectra taken with germanium (HPGe) detectors due to detector size, shape and energy resolution, background radiation, high-energy beta- or beta+ decay in the sample, beta(-)-, beta(+)- and gamma-ray backscatter, pole-zero cancellation, pulse pileup, coincidence summing, and unwanted sources of radiation.

Pharmacotherapy of social phobia.

OBJECTIVE: To review placebo-controlled medication trials in social phobia (SP). METHOD: Published and/or presented placebo-controlled trials of medication were reviewed and summarized. RESULTS: Phenelzine is effective in 60-70% of patients with SP and always superior to placebo. Although reversible inhibitors of monoamine oxidase type A (RIMAs) are safer, their benefits are unpredictable. SSRIs, fluvoxamine, paroxetine and sertraline are superior to placebo in generalized SP. Gabergic drugs are useful, e.g. clonazepam, gabapentin and pregabalin. Promising effects have been found with venlafaxine, a serotonin-norepinephrine reuptake inhibitor, and the results of larger studies should be forthcoming in the next 2 years. Drugs such as buspirone, tricyclics and beta-blockers are either ineffective or have limited use. SP is a chronic disorder, and early termination of successful pharmacotherapy is associated with a greater likelihood of relapse. Studies with paroxetine, clonazepam, sertraline and brofaromine show that continued treatment is associated with better maintenance of response. Special populations that require further study include children, those with comorbid Axis I disorders and the population with discrete (non-generalized) SP. CONCLUSION: MAOI and SSRI are most uniformly effective in treating SP. Clonazepam and gabapentin may also be useful. Other drugs are of more limited value. Long-term treatment is recommended to reduce rates of relapse.

Homeopathic constitutional type questionnaire correlates of conventional psychological and physical health scales: individual difference characteristics of young adults.

This study examined associations between scores for 19 different remedies on the constitutional type questionnaire (CTQ) and scores on standardized psychological and medical trait and state scales from health psychology research. Subjects were 104 young adult American college students (mean age 20 years; 67% female). Scales included the chemical intolerance index (CII) for environmental sensitivity, the NEO personality inventory, Marlowe-Crowne social desirability (MCSD) Scale for defensiveness, Harvard parental caring scale (HPCS) for perceived mother and father traits, Profile of Mood State (POMS) scale, Pennebaker symptom checklist (PSC), and a 3-item global health rating scale. The majority of CTQ constitutional type scores correlated significantly with greater NEO neuroticism, lower MCSD defensiveness, and greater psychological distress on the POMS subscales. NEO Extraversion and Openness subscales correlated with specific CTQ scores in directions consistent with clinical remedy pictures. CTQ Carcinosin differed from other remedies, showing no significant correlations with other scales. As hypothesized (a) persons high on CTQ scores for Carcinosin and low in parental caring (HPCS) had the highest symptom score; (b) those high on CTQ scores for Sulphur and low on HPCS had the poorest global health ratings; (c) individuals high on four different CTQ type scores (Carcinosin, Lachesis, Nux vomica, Sulphur) and high on environmental sensitivity (CII) exhibited the highest symptom scores. Taken together, the data offer additional validation of the CTQ and provide a foundation for studying interactions of constitutional type with both psychosocial and physicochemical environmental factors in homeopathic provers and patients.

A placebo-controlled study of Kava kava in generalized anxiety disorder.

We assessed the efficacy and safety of a botanical anxiolytic, Kava kava (Piper methysticum), in treating generalized anxiety disorder (GAD). Thirty-seven adults with DSM-IV GAD were randomly assigned to 4 weeks of double-blind treatment with kava or a matching placebo. Weekly efficacy assessments [Hamilton Anxiety Scale, Hospital Anxiety and Depression Scale (HADS), Self Assessment of Resilience and Anxiety (SARA)] and safety evaluations were conducted. Improvement was observed with both treatments but no differences were found in the principal analysis. Post-hoc analyses revealed significant differences based on baseline anxiety severity, whereby kava was superior on the SARA in low anxiety and placebo was superior on the HADS and SARA in high anxiety. Both treatments were well tolerated. Although kava was not superior to placebo, it would be premature to rule it out as efficacious in GAD.

Characterizing the effects of sertraline in post-traumatic stress disorder.

BACKGROUND: Sertraline has a proved efficacy in post-traumatic stress disorder (PTSD), but it is unknown which symptoms respond or in what sequence this occurs. Such information might be useful clinically and heuristically. METHOD: The study examined the effects of sertraline on the individual symptoms of PTSD. It also examined whether early changes in anger explained drug-induced change in other symptoms over time. Mixed models analysis was applied to datasets from two 12-week placebo-controlled trials of sertraline. A validated self-rating scale (DTS) was used to assess treatment efficacy. RESULTS: Sertraline was superior to placebo on 15 of 17 symptoms, especially in the numbing and hyperarousal clusters. A strong effect was found on anger from week 1, which partly explained the subsequent effects of sertraline on other symptoms, some of which began to show significantly greater response to drug than to placebo at week 6 (emotional upset at reminders, anhedonia, detachment, numbness, hypervigilance) and week 10 (avoidance of activities, foreshortened future). CONCLUSIONS: Sertraline exercises a broad spectrum effect in PTSD. Effects are more apparent on the psychological rather than somatic symptoms of PTSD, with an early modulation of anger and, perhaps, other affects, preceding improvement in other symptoms.

Paroxetine for social anxiety and alcohol use in dual-diagnosed patients.

The objective of this study was to compare the efficacy and tolerability of paroxetine to matched placebo in adults with co-occurring social anxiety disorder and alcohol use disorder. Outcome measures included standardized indices of social anxiety and alcohol use. Fifteen individuals meeting DSM-IV criteria for both social anxiety disorder and alcohol use disorder were randomized to treatment. Paroxetine (n = 6) or placebo (n = 9) was given in a double-blind format for 8 weeks using a flexible dosing schedule. Dosing began at 20 mg/d and increased to a target dose of 60 mg/d. There was a significant effect of treatment group on social anxiety symptoms, where patients treated with paroxetine improved more than those treated with placebo on both the Clinical Global Index (CGI) and the Liebowitz Social Anxiety Scale (Ps < or = 0.05). On alcohol use, there was not a significant effect of treatment on quantity/frequency measures of drinking, but there was for the CGI ratings (50% paroxetine patients versus 11% placebo patients were improvers on drinking, P < or = 0.05). This pilot study suggests that paroxetine is an effective treatment for social anxiety disorder in individuals with comorbid alcohol problems, and positive treatment effects can be seen in as little as 8 weeks. Further study is warranted to investigate its utility in helping affected individuals reduce alcohol use.

Impact of generalized social anxiety disorder in managed care.

OBJECTIVE: The authors determined the costs associated with generalized social anxiety disorder in a managed care setting. METHOD: A three-phase mail and telephone survey was conducted from July to October 1998 in two outpatient clinics of a large health maintenance organization (HMO). The survey assessed direct costs, indirect costs, health-related quality of life, and clinical severity associated with generalized social anxiety disorder, both alone and with comorbid psychopathology. RESULTS: The weighted prevalence rate of current generalized social anxiety disorder was 8.2%. In the past year, only 0.5% of subjects with generalized social anxiety disorder had been accurately diagnosed. Yet 44.1% had a mental health specialty visit or had been prescribed an antidepressant, and psychiatric comorbidity was found in 43.6%. Noncomorbid generalized social anxiety disorder was associated with significantly lower health-related quality of life, work productivity, and earnings and greater utilization of health services; generalized social anxiety disorder with comorbid psychopathology was even more disabling. Suicide was attempted by 21.9% of subjects with noncomorbid generalized social anxiety disorder. Persons with average-severity generalized social anxiety disorder had probabilities of graduating from college that were 10 percentage points lower, earned wages that were 10% lower, and had probabilities of holding a technical, professional, or managerial job that were 14 percentage points lower than the comparison group. CONCLUSIONS: In a community cohort of HMO members, generalized social anxiety disorder was rarely diagnosed or treated despite being highly prevalent and associated with significant direct and indirect costs, comorbid depression, and impairment.

Symptomatic and functional assessment of social anxiety disorder in adults.

There are several old and new tools for assessment of generalized SAD but few for nongeneralized SAD. Scales are available in both self-rated and interviewer-rated formats. Self-rated scales vary in appearance in length and specificity for SAD and psychometric properties. The best-studied self-rated scales are the FQ, FNE, SAAD, SPAI, and SPIN. The FQ is an early scale, with a subscale of social phobia with reasonable psychometric properties and has withstood the test of time. The FNE and SAAD are based on cognitive models of SAD but lack assessment of physiologic arousal symptoms--an important symptom cluster of SAD. The SPIN is a relatively new scale and shows potential especially with its three-item screener for generalized SAD. The two interviewer-rated scales, the LSAS and BSPS, are both widely used and demonstrate sound psychometric properties. Either one can be regarded as a satisfactory scale in the assessment of symptom severity and treatment response. The BSPS also measures several physical symptoms common in SAD. There are fewer validated tools available for nongeneralized SAD. It is a prevalent condition that may account for 25% or more of patients with SAD. More research is required on the epidemiology, recognition, assessment, and treatment of nongeneralized SAD. Education of patients and clinicians, and the use of improved and briefer tools in these settings, may help SAD patients to obtain appropriate help and improve their functioning and productivity. Few tools are available that can reliably assess disability due to SAD, and more research in this area is important and required.