Clinical care of childhood sexual abuse: a systematic review and critical appraisal of guidelines from European countries.

Background: The clinical management of Child sexual abuse (CSA) demands specialised skills from healthcare professionals due to its sensitivity, legal implications, and serious physical health and mental health effects. Standardised, comprehensive clinical practice guidelines (CPGs) may be pivotal. In this systematic review, we examined existing CSA national CPGs (NCPGs) from European countries to assess their quality and reporting. Methods: We systematically searched six international databases and multiple grey literature sources, reporting by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Eligible guidelines were CSA guidance from national health agencies or societies in 34 COST Action 19106 Network Countries (CANC), published between January 2012 and November 2022. Two independent researchers searched, screened, reviewed, and extracted data. NCPGs were compared for completeness with reference WHO 2017 and 2019 guidelines. We used the Appraisal of Guidelines for Research and Evaluation (AGREE II) to appraise quality and reporting. PROSPERO: CRD42022320747. Findings: Of 2919 records identified by database searches, none met inclusion criteria. Of 4714 records identified by other methods, 24 NCPGs from 17 (50%) of CANC countries were included. In 17 (50%) of eligible countries, no NCPGs were found. Content varied significantly within and between countries. NCPGs lacked many components in state-of-the art clinical practice compared to WHO reference standards, particularly in safety and risk assessment, interactions with caregivers, and mental health interventions. Appraisal by AGREE II revealed shortcomings in NCPG development, regarding scientific rigour, stakeholder involvement, implementation and evaluation. Interpretation: A notable number of European countries lack an NCPG; existing NCPGs often fall short. The healthcare response to CSA in Europe requires a coordinated approach to develop and implement high-quality CPGs. We advocate for a multidisciplinary team to develop a pan-European CSA guideline to ensure quality care for survivors. Funding: Funding was provided by the International Centre for Missing and Exploited Children.

Nine out of ten samples were mistakenly switched by The Orang-utan Genome Consortium.

The Sumatran orang-utan (Pongo abelii) reference genome was first published in 2011, in conjunction with ten re-sequenced genomes from unrelated wild-caught individuals. Together, these published data have been utilized in almost all great ape genomic studies, plus in much broader comparative genomic research. Here, we report that the original sequencing Consortium inadvertently switched nine of the ten samples and/or resulting re-sequenced genomes, erroneously attributing eight of these to the wrong source individuals. Among them is a genome from the recently identified Tapanuli (P. tapanuliensis) species: thus, this genome was sequenced and published a full six years prior to the species' description. Sex was wrongly assigned to five known individuals; the numbers in one sample identifier were swapped; and the identifier for another sample most closely resembles that of a sample from another individual entirely. These errors have been reproduced in countless subsequent manuscripts, with noted implications for studies reliant on data from known individuals.

Author Correction: Exome sequencing of Finnish isolates enhances rare-variant association power.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Exome sequencing of Finnish isolates enhances rare-variant association power.

Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exome sequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits. Exome-wide association studies for 64 quantitative traits identified 26 newly associated deleterious alleles. Of these 26 alleles, 19 are either unique to or more than 20 times more frequent in Finnish individuals than in other Europeans and show geographical clustering comparable to Mendelian disease mutations that are characteristic of the Finnish population. We estimate that sequencing studies of populations without this unique history would require hundreds of thousands to millions of participants to achieve comparable association power.

Inclusion of a specific prompt within the standard clinical pro forma used in assessment of patients referred to a child and adolescent sexual assault treatment service: A suggested safety-net to facilitate detection of other children at risk of child sexual abuse.

BACKGROUND: Evaluation of an index case of child abuse necessitates risk assessment of other children who could be vulnerable to abuse from the same perpetrator/s. OBJECTIVE: To determine the effectiveness of the addition of a prompt to the standard clinical pro forma used for the assessment of new referrals to a child and adolescent sexual assault treatment service in terms of impact upon detection of other at risk children. PARTICIPANTS AND SETTING: All referrals to a Child and Adolescent Sexual Assault Treatment Service, Galway, West Ireland. METHODS: Retrospective chart review of all children assessed between September 2016 and March 2017. Intervention initiated on September 1st, 2017. Prospective chart review of all children assessed between September 2017 and March 2018. Chart reviews established whether potential risk to siblings, and other close child contacts, of the index case had been adequately considered. RESULTS: Comparing pre and post intervention groups, documentation of children at risk significantly increased from 70% to 96% (p = 0.0124). Cases in which a letter was sent to social services regarding other "at risk" children also significantly increased from 50% to 92% (p = 0.0005). There was a change in the percentage of "at risk" children examined or planned for examination, from 66% to 84%, however that was not statistically significant (p = 0.80). CONCLUSIONS: Introduction of a simple prompt within the standard clinical pro forma had a significant positive impact upon clinicians' consideration of other "at risk" children. We suggest that other services consider including a similar section in their own pro forma documents.

Process monitoring of an HIV treatment as prevention program in British Columbia, Canada.

BACKGROUND: In light of accumulated scientific evidence of the secondary preventive benefits of antiretroviral therapy, a growing number of jurisdictions worldwide have formally started to implement HIV Treatment as Prevention (TasP) programs. To date, no gold standard for TasP program monitoring has been described. Here, we describe the design and methods applied to TasP program process monitoring in British Columbia (BC), Canada. METHODS: Monitoring indicators were selected through a collaborative and iterative process by an interdisciplinary team including representatives from all 5 regional health authorities, the BC Centre for Disease Control (BCCDC), and the BC Centre for Excellence in HIV/AIDS (BC-CfE). An initial set of 36 proposed indicators were considered for inclusion. These were ranked on the basis of 8 criteria: data quality, validity, scientific evidence, informative power of the indicator, feasibility, confidentiality, accuracy, and administrative requirement. The consolidated list of indicators was included in the final monitoring report, which was executed using linked population-level data. RESULTS: A total of 13 monitoring indicators were included in the BC TasP Monitoring Report. Where appropriate, indicators were stratified by subgroups of interest, including HIV risk group and demographic characteristics. Six Monitoring Reports are generated quarterly: 1 for each of the regional health authorities and a consolidated provincial report. CONCLUSIONS: We have developed a comprehensive TasP process monitoring strategy using evidence-based HIV indicators derived from linked population-level data. Standardized longitudinal monitoring of TasP program initiatives is essential to optimize individual and public health outcomes and to enhance program efficiencies.

Increasing incidence of bilateral mastectomies: the patient perspective.

BACKGROUND: Numerous studies have reported increasing rates of contralateral prophylactic mastectomies (CPMs). Understanding patient rationale for the surgical choice may provide insight into this trend. METHODS: A questionnaire was mailed to 350 mastectomy patients identified from a community health system tumor registry. RESULTS: Two hundred fifty questionnaires were received; of these, 237 had undergone mastectomy. Fifty-two percent had unilateral mastectomy (UM), and 43% had bilateral mastectomies (BMs) (6% for bilateral disease). Women younger than 60 years of age were more likely to choose BM (P = .0046). Those who had CPM were significantly more likely to make the same surgical decision (P < .0001). Reconstruction was performed in 52%, with BM patients more likely to undergo reconstruction (P = .009). Twenty-three (19%) needed unanticipated reoperation for reconstruction complications. CPM had equivalent rates of unanticipated surgery versus UM (P = .64). CONCLUSIONS: Patients choosing BMs are younger, have equivalent rates of reoperation because of reconstruction complications, and are significantly more satisfied with their decision than those who chose UM.

Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine.

OBJECTIVE: To establish the relative risks of in utero exposure to lamotrigine (LTG), sodium valproate (NaV) and carbamazepine (CBZ) monotherapy for neurodevelopment. DESIGN: Observational cohort study. PATIENTS AND METHODS: The study group consisted of children in Northern Ireland aged 9-60 months born to mothers who had enrolled with the UK Epilepsy and Pregnancy Register. The control group consisted of children identified from the Child Health System database across Northern Ireland. Data were gathered on covariates recognised as influencing child development. MAIN OUTCOME MEASURES: Neurodevelopment assessed using either the Bayley Scales of Infant Development or the Griffiths Mental Development Scales. RESULTS: 210 children underwent assessment by a single researcher blinded to antiepileptic drug exposure. 23 (39.6%) children exposed in utero to NaV, 10 (20.4%) exposed to CBZ and one (2.9%) exposed to LTG had evidence of mild or significant developmental delay, compared to two (4.5%) children in the control group. Multivariable analysis demonstrated that in utero exposure to NaV (OR 26.1, 95% CI 4.9 to 139; p<0.001) and to CBZ (OR 7.7, 95% CI 1.4 to 43.1; p<0.01) but not to LTG had a significant detrimental effect on neurodevelopment. CONCLUSION: In utero exposure to LTG did not have the detrimental effect on child development that was seen with NaV and with CBZ.

Comparative and demographic analysis of orang-utan genomes.

'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.

Signatures of adaptation to obligate biotrophy in the Hyaloperonospora arabidopsidis genome.

Many oomycete and fungal plant pathogens are obligate biotrophs, which extract nutrients only from living plant tissue and cannot grow apart from their hosts. Although these pathogens cause substantial crop losses, little is known about the molecular basis or evolution of obligate biotrophy. Here, we report the genome sequence of the oomycete Hyaloperonospora arabidopsidis (Hpa), an obligate biotroph and natural pathogen of Arabidopsis thaliana. In comparison with genomes of related, hemibiotrophic Phytophthora species, the Hpa genome exhibits dramatic reductions in genes encoding (i) RXLR effectors and other secreted pathogenicity proteins, (ii) enzymes for assimilation of inorganic nitrogen and sulfur, and (iii) proteins associated with zoospore formation and motility. These attributes comprise a genomic signature of evolution toward obligate biotrophy.

Combination therapy with flupirtine and opioid: open-label case series in the treatment of neuropathic pain associated with cancer.

OBJECTIVES: This study is a case series that was designed to provide data on the efficacy and the incidence and duration of adverse effects of flupirtine in the treatment of cancer-related neuropathic pain. DESIGN: This was an 8-day, open-label study of palliative care patients with neuropathic pain despite maximal opioid treatment. They received an initial dose of flupirtine 100 mg orally four times daily (QID) that could be titrated. Efficacy measures included: a neuropathic pain discriminant score; scales measuring average pain and quality of life activities; and a score of percentage pain relief. RESULTS: Ten patients were recruited. Only one patient was withdrawn because of side effects. Several pain measurements were used. All patients were able to participate in these measurements apart from two who did not understand the concept of percentage pain relief. There were significant reductions of average pain (P < 0.01) and neuropathic pain discriminant scores (P < 0.01), as well as an increase in percentage pain relief (P < 0.01). There was no statistically significant change in overall opioid use but 8/10 patients had some reduction in opioid use and three of those required substantially reduced doses of opioid when flupirtine was added to their treatment regime. Eight patients elected to continue to take flupirtine after the trial, two taking 200 mg QID and the others 100 mg QID. Of these eight, six said that flupirtine was of considerable help and two said it helped a little. All of these continued to take flupirtine with very good pain control until death, one of which was 18 months after the trial course. CONCLUSIONS: These results in humans follow animal studies that suggest a role for flupirtine in the treatment of neuropathic pain. This short duration open-label study in 10 subjects suggests that flupirtine may be useful in the treatment of neuropathic pain when used in combination with opioids.

Real-world application of breast-specific gamma imaging, initial experience at a community breast center and its potential impact on clinical care.

BACKGROUND: Breast-specific gamma imaging (BSGI) has brought scintimammography back to the forefront by using a dedicated small field-of-view system designed to detect and localize lesions down to 2 mm. Initial studies have reported sensitivity equaling that of magnetic resonance imaging, but with improved specificity. We reviewed our initial experience to evaluate the impact of this technology at our community breast center. METHODS: We performed a retrospective review of the initial 176 patients who underwent BSGI. RESULTS: A total of 128 patients underwent BSGI because of suspicious imaging, abnormal physical examination, or high risk with dense breasts. BSGI was positive in 12 of 107 patients with breast imaging reporting and data system (BI-RADS) 1, 2, or 3. Two of these were cancer. Of the 21 patients with BI-RADS 4, 18 were BSGI negative (11 with benign biopsy, 7 observed), and 3 were BSGI positive with 2 being cancer. Forty-eight patients with a new diagnosis of cancer obtained BSGI for further work-up. It was positive at a new location in 6 cases: 2 cases were new cancers in the contralateral breast, 1 was in the ipsilateral breast, and the remaining 3 had benign pathology. Of the 176 initial patients, clinical management was changed significantly in 14.2%, with another 6.3% in whom a negative BSGI could have prevented a biopsy. CONCLUSIONS: BSGI has played an important role in our clinical management of breast patients with complex breast tissue. BSGI is also a good adjunctive imaging tool in the work-up of newly diagnosed breast cancer patients.

Risk counseling and management in patients with lobular carcinoma in situ.

BACKGROUND: The understanding of lobular carcinoma in situ (LCIS) has evolved since it was first described. LCIS once was thought to be a premalignant condition, but now it is considered a marker for increased risk for developing invasive breast cancer. We evaluated patient perception of risk, counseling, and subsequent management. METHODS: A community cancer registry of 3,605 cases of breast cancer was reviewed. Fifty-five (1.5%) patients with LCIS as their sole diagnosis were identified and these patients were sent a questionnaire. RESULTS: Forty of 55 patients completed the questionnaire for a 73% response rate. The patients' perception of lifetime risk for invasive cancer was variable. Surgeons performed the majority of counseling. Fourteen patients (35%) were placed on a selective estrogen-receptor modulator. Eleven patients (28%) had bilateral mastectomy. Three patients had unilateral mastectomy. Screening recommendations included an annual mammography (64%), a professional examination (64%), and a monthly self-breast examination (75%). CONCLUSION: A patient's perception of risk for invasive breast cancer after a diagnosis of LCIS is widely variable. Patients will adhere to suggested screening recommendations. Surgeons are performing the majority of counseling and must stay abreast on current recommendations.

Geographic variation in sentinel node adaptation by practicing surgeons in Oregon.

BACKGROUND: The sentinel node biopsy (SNB) technique is an important tool in the diagnosis and treatment of breast cancer and melanoma. However, surgeons in Oregon have not universally adopted its use. METHODS: Mailed questionnaire. RESULTS: The response rate was 32%. Seventy-four (76%) of the surgical respondents perform routine SNB; 49% completed courses, and 32% learned the technique in residency. Sixty-one (89%) performed axillary dissection with their initial cases. It took 21 of 40 (52%) surgeons greater than a year to accrue 20 cases. Of 23 surgeons (24%) not performing SNB, 89% believed it was an important skill to obtain, and 70% thought they would benefit from proctoring opportunities. Six (26%) did not have technological support at their hospital. Surgeons at hospitals with less than 50 beds (P = .001) and at rural hospitals (P = .003) were less likely to perform SNB. CONCLUSION: The majority of urban general surgeons in Oregon use SNB in their practice. However, the incorporation of SNB for surgeons practicing in smaller hospitals and rural settings is less frequent than in the urban environment. As SNB becomes the standard of care, we need to overcome these barriers so that patients can have access to this procedure in their own communities.

Perspective on reconstruction after mastectomy.

BACKGROUND: We sought to evaluate the factors influencing our patients to receive or forego reconstruction after mastectomy and their subsequent satisfaction with their decision. METHODS: A questionnaire was sent to 819 patients who underwent mastectomy from 1994 to 1998 in a community-based health system. RESULTS: Response rate was 50% (408 of 819). Overall, 92% (n = 243) of women who did not have reconstruction and 89% (n = 152) of women who did proceed with reconstruction were happy with their decision. Fifty-five (17%) respondents were not offered reconstruction. For this group, age was a significant factor as 64% of them were 60 years or older (P < 0.0001). Dissatisfied patients were disappointed with their cosmetic, sensory, or functional outcome. Their result did not meet their expectations. There were no significant differences noted on the basis of marital status. CONCLUSION: Ninety percent of patients adjust well to mastectomy whether or not they receive reconstruction if they make informed decisions with realistic expectations. Surgeons should offer reconstruction to women of all ages although patients over 60 years old are less likely to proceed with, and complete, reconstruction.