Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome: 12-Month Follow-Up of a Randomized Clinical Trial.

Importance: Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. Objective: To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. Design, Setting, And Participants: This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. Interventions: A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. Main Outcomes And Measures: The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). Results: In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79 000. Conclusions And Relevance: There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature. Trial Registration: ClinicalTrials.gov Identifier: NCT03916055.

Cost-effectiveness of semaglutide 2.4 mg in chronic weight management in Portugal.

BACKGROUND: Obesity and overweight are a significant public health concern. Subcutaneous semaglutide 2.4 mg injection is a glucagon-like peptide-1 (GLP-1) analogue approved by the European Medicines Agency as an adjunct to a reduced calorie diet and increased physical activity (diet and exercise, D&E) for the treatment obesity and overweight in the presence of at least one weight related comorbidity. This study aimed to assess the cost-effectiveness of semaglutide 2.4 mg in combination with D&E compared to D&E alone for the Portuguese setting. METHODS: Analysis were conducted using the Core Obesity Model (COM) version 18, a Markov state transition cohort model, to predict the health outcomes and costs of weight related complications based on changes in surrogate endpoints. Efficacy and safety data were sourced from the STEP trials (Body Mass Index, systolic blood pressure and glycemic status) from a cohort of adults aged on average 48 years with obesity (BMI ≥ 30 kg/m2) and ≥ 1 obesity-related comorbidities, over a time horizon of 40 years. Costs were estimated from the perspective of the Portuguese National Health Service. Sensitivity analyses were conducted to test the robustness of results across a range of assumptions. RESULTS: On a patient level, Semaglutide 2.4 mg in addition to D&E compared to D&E alone, improved QALYs by 0.098 and yielded higher costs by 1,325 EUR over a 40-year time horizon, with an ICER of 13,459 EUR per QALY gained and 100% probability of cost-effectiveness at the given WTP. Semaglutide 2.4 mg remained cost-effective across all different scenarios and sensitivity analysis at a WTP of 20,000 EUR per QALY. Among the subpopulations examined, Semaglutide 2.4 mg yielded ICERs of 18,459 EUR for patients with BMI ≥ 30 kg/m2 and of 22,657 EUR for patients with BMI ≥ 35 kg/m2. CONCLUSIONS: Semaglutide 2.4 mg was cost-effective compared to D&E alone for patients with obesity (BMI ≥ 30 kg/m2) and weight related comorbidities in Portugal, over a 40-year time horizon.

Study protocol for a single-blind, parallel-group, randomised, controlled non-inferiority trial of 4-day intensive versus standard cognitive behavioural therapy for adults with obsessive-compulsive disorder.

INTRODUCTION: Individual cognitive behavioural therapy (CBT) with exposure and response prevention is an effective treatment for obsessive-compulsive disorder (OCD). However, individual CBT is costly and time-consuming, requiring weekly therapy sessions for 3-4 months. A 4-day intensive version of CBT for OCD delivered in group format has been recently developed in Norway (Bergen 4-day treatment, B4DT). B4DT has shown promising results in several uncontrolled and one small, randomised trial, but its non-inferiority to the gold standard treatment has not been established. METHODS AND ANALYSIS: This single-blind, randomised controlled trial including 120 patients (60 per arm) will compare B4DT to individual CBT. The primary outcome is the blind assessor-rated Yale-Brown Obsessive Compulsive Scale (Y-BOCS). We hypothesise that B4DT will be non-inferior to gold standard CBT 15 weeks after treatment start. The non-inferiority margin is set at four points on the Y-BOCS. Secondary outcomes include time to treatment response, cost-effectiveness, response and remission rates, drop-out rates and adverse events. ETHICS AND DISSEMINATION: This study has been approved by the Swedish Ethical Review Authority. Hypotheses were specified and analysis code published before data collection started. Results from all analyses will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials and Consolidated Health Economic Evaluation Reporting Standards irrespective of outcome. TRIAL REGISTRATION NUMBER: NCT05608278.

Adverse drug reactions in hospitals: population estimates for Portugal and the ICD-9-CM to ICD-10-CM crosswalk.

BACKGROUND: Adverse drug reactions (ADR), both preventable and non-preventable, are frequent and pose a significant burden. This study aimed to produce up-to-date estimates for ADR rates in hospitals, in Portugal, from 2010 to 2018. In addition, it explores possible pitfalls when crosswalking between ICD-9-CM and ICD-10-CM code sets for ADR identification. METHODS: The Portuguese Hospital Morbidity Database was used to identify hospital episodes (outpatient or inpatient) with at least one ICD code of ADR. Since the study period spanned from 2010 to 2018, both ICD-9-CM and ICD-10-CM codes based on previously published studies were used to define episodes. This was an exploratory study, and descriptive statistics were used to provide ADR rates and summarise episode features for the full period (2010-2018) as well as for the ICD-9-CM (2010-2016) and ICD -10-CM (2017-2018) eras. RESULTS: Between 2010 and 2018, ADR occurred in 162,985 hospital episodes, corresponding to 1.00% of the total number of episodes during the same period. Higher rates were seen in the oldest age groups. In the same period, the mean annual rate of episodes related to ADR was 174.2/100,000 population. The episode rate (per 100,000 population) was generally higher in males, except in young adults (aged '15-20', '25-30' and '30-35' years), although the overall frequency of ADR in hospital episodes was higher in females. CONCLUSIONS: Despite the ICD-10-CM transition, administrative health data in Portugal remain a feasible source for producing up-to-date estimates on ADR in hospitals. There is a need for future research to identify target recipients for preventive interventions and improve medication safety practices in Portugal.

Impact of developmental coordination disorder in childhood on educational outcomes in adulthood among neonatal intensive care recipients: a register-based longitudinal cohort study.

OBJECTIVES: Developmental coordination disorder (DCD) is related to poorer educational outcomes among children and adolescents. Evidence on this association into adulthood is lacking. Therefore, we aimed to investigate whether probable DCD (pDCD) in childhood affected educational outcomes among adults, and whether this was affected by sex or a co-occurring attention deficit in childhood. DESIGN: Register-based longitudinal cohort study. SETTING: Neonatal intensive care (NIC) recipients born at Uppsala University Children's Hospital, Uppsala, Sweden, from 1986 to 1989 until they reached the age of 28. PARTICIPANTS: 185 NIC recipients. PRIMARY AND SECONDARY OUTCOME MEASURES: At the age of 6.5, 46 (24.6%) of the NIC recipients were diagnosed with pDCD. Using register-based longitudinal data, we compared participants with and without pDCD in terms of: (1) age at Upper Secondary School (USS) graduation, and (2) highest level of education achieved by age 28. RESULTS: The median age at USS graduation was 19 years, with similar graduation ages and ranges between those with or without pDCD. However, a higher proportion of participants without pDCD had graduated from USS at ages 19 and 24. By age 29, most participants had completed USS. At age 28, 33% of participants had attained a bachelor's or master's degree. Although there was no significant difference between the groups, the proportion that had attained a degree was higher among those without pDCD and women without pDCD had achieved the highest level of education. Educational outcomes remained similar for those with pDCD, regardless of childhood attention deficit. CONCLUSIONS: pDCD during childhood may have a lasting impact on educational outcomes, particularly among women. Raising awareness of DCD among parents, health and educational professionals is vital for early identification and the provision of appropriate support and interventions in schools, mitigating the potential negative consequences associated with DCD and promoting positive educational outcomes.

The cost-effectiveness of a virtual intervention to prevent eating disorders in young women in Sweden.

OBJECTIVE: To determine the cost-effectiveness of a virtual version of the Body Project (vBP), a cognitive dissonance-based program, to prevent eating disorders (ED) among young women with a subjective sense of body dissatisfaction in the Swedish context. METHOD: A decision tree combined with a Markov model was developed to estimate the cost-effectiveness of the vBP in a clinical trial population of 149 young women (mean age 17 years) with body image concerns. Treatment effect was modeled using data from a trial investigating the effects of vBP compared to expressive writing (EW) and a do-nothing alternative. Population characteristics and intervention costs were sourced from the trial. Other parameters, including utilities, treatment costs for ED, and mortality were sourced from the literature. The model predicted the costs and quality-adjusted life years (QALYs) related to the prevention of incidence of ED in the modeled population until they reached 25 years of age. The study used both a cost-utility and return on investment (ROI) framework. RESULTS: In total, vBP yielded lower costs and larger QALYs than the alternatives. The ROI analysis denoted a return of US $152 for every USD invested in vBP over 8 years against the do-nothing alternative and US $105 against EW. DISCUSSION: vBP is likely to be cost-effective compared to both EW and a do-nothing alternative. The ROI from vBP is substantial and could be attractive information for decision makers for implementation of this intervention for young females at risk of developing ED. PUBLIC SIGNIFICANCE: This study estimates that the vBP is cost-effective for the prevention of eating disorders among young women in the Swedish setting, and thus is a good investment of public resources.

Economic evaluation of telemonitoring as a follow-up approach for patients with obstructive sleep apnea syndrome starting treatment with continuous positive airway pressure.

Telemonitoring of obstructive sleep apnea patients is increasingly being adopted though its cost-effectiveness evidence base is scanty. This study investigated whether telemonitoring is a cost-effective strategy compared with the standard follow-up in patients with obstructive sleep apnea who are starting continuous positive airway pressure treatment. In total, 167 obstructive sleep apnea patients were randomised into telemonitoring (n = 79) or standard follow-up (n = 88), initiated continuous positive airway pressure treatment, and were followed up for 6 months. The frequencies of healthcare contacts, related costs (in USD 2021 prices), treatment effect and compliance were compared between the follow-up approaches using generalised linear models. The cost effectiveness analysis was conducted from a healthcare perspective and the results presented as cost per avoided extra clinic visit. Additionally, patient satisfaction between the two approaches was explored. The analysis showed no baseline differences. At follow-up, there was no significant difference in treatment compliance, and the mean residual apnea-hypoapnea index. There was no difference in total visits, adjusted incidence rate ratio 0.87 (0.72-1.06). Participants in the telemonitoring arm made eight times more telephone visits, 8.10 (5.04-13.84), and about 73% fewer physical healthcare visits 0.27 (0.20-0.36). This translated into significantly lower total costs for the telemonitoring approach compared with standard follow-up, -192 USD (-346 to -41). The form of follow-up seemed to have no impact on the extent of patient satisfaction. These results demonstrate the telemonitoring of patients with obstructive sleep apnea initiating continuous positive airway pressure treatment as a cost saving strategy and can be argued as a potential worthy investment.

Health and economic outcomes of a universal early intervention for parents and children from birth to age five: evaluation of the Salut Programme using a natural experiment.

BACKGROUND: The aim of this study was to investigate the health and economic outcomes of a universal early intervention for parents and children, the Salut Programme, from birth to when the child completed five years of age. METHODS: This study adopted a retrospective observational design using routinely collected linked register data with respect to both exposures and outcomes from Västerbotten county, in northern Sweden. Making use of a natural experiment, areas that received care-as-usual (non-Salut area) were compared to areas where the Programme was implemented after 2006 (Salut area) in terms of: (i) health outcomes, healthcare resource use and costs around pregnancy, delivery and birth, and (ii) healthcare resource use and related costs, as well as costs of care of sick child. We estimated total cumulative costs related to inpatient and specialised outpatient care for mothers and children, and financial benefits paid to mothers to stay home from work to care for a sick child. Two analyses were conducted: a matched difference-in difference analysis using the total sample and an analysis including a longitudinal subsample. RESULTS: The longitudinal analysis on mothers who gave birth in both pre- and post-measure periods showed that mothers exposed to the Programme had on average 6% (95% CI 3-9%) more full-term pregnancies and 2% (95% CI 0.03-3%) more babies with a birth weight ≥ 2500 g, compared to mothers who had care-as-usual. Savings were incurred in terms of outpatient care costs for children of mothers in the Salut area ($826). The difference-in-difference analysis using the total sample did not result in any significant differences in health outcomes or cumulative resource use over time. CONCLUSIONS: The Salut Programme achieved health gains, as a health promotion early intervention for children and parents, in terms of more full-term pregnancies and more babies with a birth weight ≥ 2500 g, at reasonable cost, and may lead to lower usage of outpatient care. Other indicators point towards positive effects, but the small sample size may have led to underestimation of true differences.

A near-complete species-level phylogeny of uropeltid snakes harnessing historical museum collections as a DNA source.

Uropeltidae is a clade of small fossorial snakes (ca. 64 extant species) endemic to peninsular India and Sri Lanka. Uropeltid taxonomy has been confusing, and the status of some species has not been revised for over a century. Attempts to revise uropeltid systematics and undertake evolutionary studies have been hampered by incompletely sampled and incompletely resolved phylogenies. To address this issue, we take advantage of historical museum collections, including type specimens, and apply genome-wide shotgun (GWS) sequencing, along with recent field sampling (using Sanger sequencing) to establish a near-complete multilocus species-level phylogeny (ca. 87% complete at species level). This results in a phylogeny that supports the monophyly of all genera (if Brachyophidium is considered a junior synonym of Teretrurus), and provides a firm platform for future taxonomic revision. Sri Lankan uropeltids are probably monophyletic, indicating a single colonisation event of this island from Indian ancestors. However, the position of Rhinophis goweri (endemic to Eastern Ghats, southern India) is unclear and warrants further investigation, and evidence that it may nest within the Sri Lankan radiation indicates a possible recolonisation event. DNA sequence data and morphology suggest that currently recognised uropeltid species diversity is substantially underestimated. Our study highlights the benefits of integrating museum collections in molecular genetic analyses and their role in understanding the systematics and evolutionary history of understudied organismal groups.

A Rare and Surprising Case of Spontaneous Type B Carotid-Cavernous Fistula in an Internal Medicine Ward.

Carotid-cavernous fistulas are abnormal communications between the carotid arteries and the cavernous sinus. They can be spontaneous, which is rare, or acquired, most often post-traumatic. We describe the case of a 59-year-old woman with complaints of right-sided red eye and blurred vision that did not improve with antibiotic treatment for bacterial conjunctivitis, progressing to what appeared to be post-septal cellulitis. The patient had exuberant chemosis, diplopia, VI cranial nerve palsy, and elevated intraocular pressure in the right eye. Computed tomography of the orbits showed right-sided thickening of the soft tissues of the upper eyelid and the medial and lateral rectus muscles, and an enlargement of the ipsilateral superior ophthalmic vein. However, antibiotics did not cause any kind of improvement. After a laborious diagnostic march, the diagnosis of a rare case of Barrow type B spontaneous carotid-cavernous fistula was confirmed. The patient underwent confirmatory angiography with endovascular treatment at the same time, showing rapid improvement after the procedure, without any sequelae. It is of great importance that clinicians are alert to this diagnosis, as diagnostic and therapeutic delay can lead to severe ocular compromise. In patients with a presumptive diagnosis of conjunctivitis and/or orbital cellulitis that does not improve with antibiotic treatment, the differential diagnosis with this rare entity should be considered, so that the appropriate treatment can be timely instituted.

Introduction of specialized heart failure nurses in primary care and its impact on readmissions.

BACKGROUND: Heart failure (HF) has a 2% prevalence in the population and is a major cause of morbidity and mortality. Multiple efforts have been made worldwide to improve quality of care and decrease unplanned readmissions for HF patients, one of which has been the introduction of specialist HF nurses (HFN) in primary health care. The present evidence on the benefits of HFN is contradicting. This study aims to evaluate the impact of a quality improvement intervention, availability of a HFN in Swedish primary care, on hospital readmissions. METHODS: All patients over the age of 65 with a HF diagnosis and with complete information on availability of a HFN were included in this retrospective register-based study. Using propensity score matching (PSM) techniques, two comparable groups of 128 patients each were created according to the exposure status, availability or no availability of a HFN. The rate of readmission was compared between the groups. RESULTS: Using PSM, 256 patients were matched, 128 in the HFN group and 128 in the no-HFN group. A total of 50% and 46.09% of patients in the HFN and no-HFN groups were readmitted, respectively. Mean number of readmissions per patient was 1.19 (SD 0.61) in the HFN group and 1.10 (SD 0.44) in the no-HFN group. Patients in the HFN had 17.6% higher odds of being readmitted during the study period, OR: 1.176 (CI: 0.716-1.932), and 3.8% lower odds of being readmitted within 30 days, OR: 0.962 (CI: 0.528-1.750). CONCLUSIONS: Availability of a HFN in primary care was not significantly associated with reduced readmissions for the patients included in this study. Further investigations are warranted looking at the impacts of availability and access to a HFN in primary care on readmissions and other patient outcomes.

Therapist-Supported Internet-Delivered Exposure and Response Prevention for Children and Adolescents With Tourette Syndrome: A Randomized Clinical Trial.

Importance: The availability of behavior therapy for individuals with Tourette syndrome (TS) and chronic tic disorder (CTD) is limited. Objective: To determine the efficacy and cost-effectiveness of internet-delivered exposure and response prevention (ERP) for children and adolescents with TS or CTD. Design, Setting, and Participants: This single-masked, parallel group, superiority randomized clinical trial with nationwide recruitment was conducted at a research clinic in Stockholm, Sweden. Out of 615 individuals assessed for eligibility, 221 participants meeting diagnostic criteria for TS or CTD and aged 9 to 17 years were included in the study. Enrollment began in April 2019 and ended in April 2021. Data were analyzed between October 2021 and March 2022. Interventions: Participants were randomized to 10 weeks of therapist-supported internet-delivered ERP for tics (111 participants) or to therapist-supported internet-delivered education for tics (comparator group, 110 participants). Main Outcomes and Measures: The primary outcome was change in tic severity from baseline to the 3-month follow-up as measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS). YGTSS-TTSS assessors were masked to treatment allocation. Treatment response was operationalized as a score of 1 ("Very much improved") or 2 ("Much improved") on the Clinical Global Impression-Improvement scale. Results: Data loss was minimal, with 216 of 221 participants (97.7%) providing primary outcome data. Among randomized participants (152 [68.8%] boys; mean [SD] age, 12.1 [2.3] years), tic severity improved significantly, with a mean reduction of 6.08 points on the YGTSS-TTSS in the ERP group (mean [SD] at baseline, 22.25 [5.60]; at 3-month follow-up, 16.17 [6.82]) and 5.29 in the comparator (mean [SD] at baseline, 23.01 [5.92]; at 3-month follow-up, 17.72 [7.11]). Intention-to-treat analyses showed that the 2 groups improved similarly over time (interaction effect, -0.53; 95% CI, -1.28 to 0.22; P = .17). Significantly more participants were classified as treatment responders in the ERP group (51 of 108 [47.2%]) than in the comparator group (31 of 108 [28.7%]) at the 3-month follow-up (odds ratio, 2.22; 95% CI, 1.27 to 3.90). ERP resulted in more treatment responders at little additional cost compared with structured education. The incremental cost per quality-adjusted life-year gained was below the Swedish willingness-to-pay threshold, at which ERP had a 66% to 76% probability of being cost-effective. Conclusions and Relevance: Both interventions were associated with clinically meaningful improvements in tic severity, but ERP led to higher response rates at little additional cost. Trial Registration: ClinicalTrials.gov identifier: NCT03916055.

The cost-effectiveness of a proportionate parenting programme for primary caregivers and their child: an economic evaluation using evidence from the E-SEE Trial.

BACKGROUND: Behavioural and mental disorders have become a public health crisis; averting mental ill-health in early years can achieve significant longer-term health benefits and cost savings. This study assesses whether the Enhancing Social-Emotional Health and Wellbeing in the Early Years (E-SEE-Steps)-a proportionate universal delivery model comprising the Incredible Babies book (IY-B) and the Incredible Years Infant (IY-I) and Toddler (IY-T) parenting programmes is cost-effective compared to services as usual (SAU) for the primary caregiver, child and dyad. METHODS: Using UK data for 339 primary caregivers from the E-SEE trial, we conducted a within-trial economic evaluation assessing the cost-effectiveness of E-SEE Steps. Health outcomes were expressed in quality-adjusted life-years (QALY) and costs in UK pounds sterling (2018-19). Missing data were populated via multiple imputation and costs and QALYs discounted at 3.5% per annum. Cost-effectiveness results were conducted for primary caregivers, children and dyad using econometric modelling to control for patient co-variables. Uncertainty was explored through scenario and sensitivity analyses. RESULTS: The average cost of E-SEE Steps intervention was £458.50 per dyad. E-SEE Steps was associated with modest gains in primary caregiver HRQoL but minor decrements in child HRQoL compared to SAU. For primary caregivers, E-SEE Steps was more effective (0.034 QALYs) and more costly (£446) compared to SAU, with a corresponding incremental cost-effectiveness ratio (ICER) of £13,011 per QALY. In children, E-SEE Steps was strictly dominated with poorer outcomes (-0.005 QALYs) and greater costs (£178) relative to SAU. QALY gains in primary caregivers exceeded those QALY losses found in children, meaning E-SEE Steps was more effective (0.031 QALYs) and costly (£621) for the dyad (ICER: £20,062 per QALY). All scenario analyses found E-SEE Steps cost-effective for the dyad at a £30,000 per QALY threshold. Sensitivity analyses found significant cost reductions from expansions in programme delivery and attendance. CONCLUSIONS: E-SEE Steps achieved modest health gains in primary caregivers but small negative effects on children and was more costly than SAU. E-SEE Steps appears cost-effective for the dyad, but the results should be interpreted with caution given the potential detrimental impact on children. TRIAL REGISTRATION: ISRCTN11079129 ; Pre participant trial enrolment, 11/05/2015.

Evidence for investing in parenting interventions aiming to improve child health: a systematic review of economic evaluations.

A comprehensive review of the economic evidence on parenting interventions targeting different aspects of child health is lacking to support decision-making. The aim of this review is to provide an up to date synthesis of the available health economic evidence for parenting interventions aiming to improve child health. A systematic review was conducted with articles identified through Econlit, Medline, PsychINFO, and ERIC databases. Only full economic evaluations comparing two or more options, considering both costs and outcomes were included. We assessed the quality of the studies using the Drummond checklist. We identified 44 studies of varying quality that met inclusion criteria; 22 targeting externalizing behaviors, five targeting internalizing problems, and five targeting other mental health problems including autism and alcohol abuse. The remaining studies targeted child abuse (n = 5), obesity (n = 3), and general health (n = 4). Studies varied considerably and many suffered from methodological limitations, such as limited costing perspectives, challenges with outcome measurement and short-time horizons. Parenting interventions showed good value for money in particular for preventing child externalizing and internalizing behaviors. For the prevention of child abuse, some programs had the potential of being cost-saving over the longer-term. Interventions were not cost-effective for the treatment of autism and obesity. Future research should include a broader spectrum of societal costs and quality-of-life impacts on both children and their caregivers.

Whipple's disease orbitopathy: case report and review of literature.

A 59-year-old female patient was diagnosed with Whipple's disease (WD) after several months of constitutional complaints and adenopathies that were initially misinterpreted as sarcoidosis. Initial treatment included doxycycline, hydroxychloroquine and prednisolone, which was suspended due to long-term clinical stability. Four months after prednisolone suspension, the patient presented with right periorbital oedema and erythema. Ophthalmological examination revealed restricted eye movements. A computed tomography (CT) scan demonstrated signs of myositis. The patient was treated with anti-inflammatory and antibiotic drugs, that induced remission of the orbitopathy. During the following two years, she presented three relapses, affecting both the right or the left eyes. The last episode was also associated with systemic corticosteroid tapering. Orbitopathy is a rare form of WD presentation and the diagnosis of this condition may be challenging. As the clinical spectrum may range from an incidentaloma to a severe compressive neuropathy, proper recognition and management of WD orbitopathy is essential.

Macular Cystoid Edema Induced by Nab-Paclitaxel.

A 61-year old male was referred to the Ophthalmology department because of decreased bilateral visual acuity. The patient had metastatic pancreatic adenocarcinoma and was being treated with gemcitabine+nab-paclitaxel. On examination, the patient presented best corrected visual acuities of 4/20 and 2/20 in the right and left eye, respectively. The optical coherence tomography revealed bilateral severe macular edema. Macular edema was considered secondary to nab-paclitaxel and the drug was discontinued. Three months after drug discontinuation, the patient presented best corrected visual acuities of 20/20 and 16/20 in the right and left eye, respectively, and normal fundoscopy. Macular edema is a very rare side effect of taxanes, and the etiopathology is still unknown. Edema is usually reversible upon discontinuation of the offending agent. Clinicians should be aware of this adverse effect of taxanes, and a high index of clinical suspicion is essential for diagnosis.

Doente do sexo masculino, de 61 anos de idade, foi encaminhado para Oftalmologia por queixas de diminuição da acuidade visual bilateral. Tratava-se de um doente com um adenocarcinoma pancreático metastizado, sob tratamento com gemcitabina+nab-paclitaxel. Ao exame oftalmológico, o doente apresentava melhores acuidades visuais corrigidas de 4/20 e 2/20 do olho direito e esquerdo, respetivamente. A tomografia de coerência ótica revelou a presença de edema macular bilateral grave. O edema macular foi considerado secundário ao uso de nab-paclitaxel, pelo que o fármaco foi suspenso. Três meses após a suspensão do fármaco, o paciente apresentava acuidades visuais de 20/20 e 16/20 do olho direito e esquerdo, respetivamente, e uma fundoscopia normal. O edema macular é um efeito adverso muito raro dos taxanos e a sua etiopatologia ainda não se encontra totalmente esclarecida. O edema é habitualmente reversível após a suspensão do agente causador. Um elevado índice de suspeição é essencial para o diagnóstico desta condição.

The cost-effectiveness of treatments for attention deficit-hyperactivity disorder and autism spectrum disorder in children and adolescents: a systematic review.

Economic evaluations can help decision makers identify what services for children with neurodevelopmental disorders provide best value-for-money. The aim of this paper is to review the best available economic evidence to support decision making for attention deficit-hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children and adolescents. We conducted a systematic review of economic evaluations of ADHD and ASD interventions including studies published 2010-2020, identified through Econlit, Medline, PsychINFO, and ERIC databases. Only full economic evaluations comparing two or more options, considering both costs and consequences were included. The quality of the studies was assessed using the Drummond checklist. We identified ten studies of moderate-to-good quality on the cost-effectiveness of treatments for ADHD and two studies of good quality of interventions for ASD. The majority of ADHD studies evaluated pharmacotherapy (n = 8), and two investigated the economic value of psychosocial/behavioral interventions. Both economic evaluations for ASD investigated early and communication interventions. Included studies support the cost-effectiveness of behavioral parenting interventions for younger children with ADHD. Among pharmacotherapies for ADHD, different combinations of stimulant/non-stimulant medications for children were cost-effective at willingness-to-pay thresholds reported in the original papers. Early intervention for children with suspected ASD was cost-effective, but communication-focused therapy for preschool children with ASD was not. Prioritizing more studies in this area would allow decision makers to promote cost-effective and clinically effective interventions for this target group.

Taxonomy and natural history of the poorly known Dindigul shieldtail Uropeltis dindigalensis (Beddome, 1877) (Serpentes: Uropeltidae).

Uropeltis dindigalensis (Beddome, 1877) is a poorly known uropeltid (shieldtail) snake from peninsular India. Here we report morphological data for 14 preserved and nine uncollected specimens, most of which have not been previously reported. We designate a lectotype from the type series, describe it, and present the first published photographs of some of the type material. Recharacterization of U. dindigalensis clarifies its taxonomic distinctiveness and its geographical distribution. We report new natural-history observations from museum specimens and of individuals in life, including viviparity and feeding behaviour. The species is known only from the higher elevations of Sirumalai hills, in the southern end of the Eastern Ghats. Uropeltis dindigalensis appears somewhat capable of tolerating low-intensity agriculture. The main immediate conservation threats are probably greater intensity human activities, including road traffic, and possibly climate change given that the species is restricted to the uppermost elevations of a small hill range. The very small extent of occurrence within a single threat-defined location (none of which lies within a protected area), combined with decreasing quality and quantity of habitat, likely qualifies U. dindigalensis as Critically Endangered (or, at best, Endangered) under IUCN Red List criteria.