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1.

Background

Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype.

Methods

We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample.

Results

Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n?=?235) versus LR-noASD group (n?=?115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition.

Conclusions

Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.
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2.

Background

Alterations in brain development during infancy may precede the behavioral manifestation of developmental disorders. Infants at increased risk for autism are also at increased risk for other developmental disorders, including, quite commonly, language disorders. Here we assess the extent to which electroencephalographic (EEG) differences in infants at high versus low familial risk for autism are present by 3 months of age, and elucidate the functional significance of EEG power at 3 months in predicting later development.

Methods

EEG data were acquired at 3 months in infant siblings of children with autism (high risk; n = 29) and infant siblings of typically developing children (low risk; n = 19) as part of a prospective, longitudinal investigation. Development across multiple domains was assessed at 6, 9, 12, 18, 24, and 36 months. Diagnosis of autism was determined at 18–36 months. We assessed relationships between 3-month-olds’ frontal EEG power and autism risk, autism outcome, language development, and development in other domains.

Results

Infants at high familial risk for autism had reduced frontal power at 3 months compared to infants at low familial risk for autism, across several frequency bands. Reduced frontal high-alpha power at 3 months was robustly associated with poorer expressive language at 12 months.

Conclusions

Reduced frontal power at 3 months may indicate increased risk for reduced expressive language skills at 12 months. This finding aligns with prior studies suggesting reduced power is a marker for atypical brain function, and infants at familial risk for autism are also at increased risk for altered developmental functioning in non-autism-specific domains.
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3.

Purpose

To compare the order of presentation of bladder and motor symptoms between multiple system atrophy phenotypes.

Methods

Medical records were retrospectively reviewed in 144 patients.

Results

Bladder symptoms occurred either before or within 12 months after onset of motor symptoms in significantly more patients with the cerebellar phenotype than the parkinsonian phenotype (80 vs. 53%, p = 0.003); similar results were observed for urinary incontinence (79 vs. 45%, p = 0.001).

Conclusions

Urinary dysfunction is more likely to appear either before or shortly after motor symptoms in the cerebellar phenotype than in the parkinsonian phenotype.
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4.

Background

Recent research has demonstrated that subclinical autistic traits of parents amplify the effects of deleterious mutations in the causation of autism spectrum disorder (ASD) in their offspring. Here, we examined the extent to which two neurodevelopmental traits that are non-specific to ASD—inattention/hyperactivity and motor coordination—might contribute to ASD recurrence in siblings of ASD probands.

Methods

Data from a quantitative trait study of 114 ASD probands and their brothers, 26% of whom also had ASD, were analyzed. Autistic trait severity was ascertained using the Social Responsiveness Scale-2, attention/hyperactivity problems using the Achenbach System of Empirically Based Assessment, and motor coordination (in a subset of participants) using the Developmental Coordination Disorder Questionnaire.

Results

Among siblings (affected and unaffected), both categorical recurrence of ASD (Nagelkerke R 2 = 0.53) and quantitative ASD trait burden (R 2 = 0.55) were predicted by sibling ADHD and motor coordination impairment scores, even though these traits, on average, were not elevated among the unaffected siblings.

Conclusions

These findings in a clinical family cohort confirm observations from general population studies that inattention/hyperactivity and motor impairment—axes of behavioral development that are non-specific to ASD, and often appreciable before ASD is typically diagnosed—jointly account for over 50% of the variation in autistic impairment of siblings, whether ascertained quantitatively or categorically. This finding within a sibling design suggests that background ASD susceptibilities that are inherited but non-specific (“BASINS”) may contribute to additive genetic liability in the same manner that ASD-specific susceptibilities (such as parental subclinical ASD traits and deleterious mutations) engender ASD risk.
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5.

Objective

This study assessed whether children clinically referred for gender dysphoria (GD) show symptoms that overlap with Autism Spectrum Disorder (ASD). Circumscribed preoccupations/intense interests and repetitive behaviors were considered as overlapping symptoms expressed in both GD and ASD.

Methods

To assess these constructs, we examined Items 9 and 66 on the Teacher’s Report Form (TRF), which measure obsessions and compulsions, respectively.

Results

For Item 9, gender-referred children (n = 386) were significantly elevated compared to the referred (n = 965) and non-referred children (n = 965) from the TRF standardization sample. For Item 66, gender-referred children were elevated in comparison to the non-referred children, but not the referred children.

Conclusions

These findings provided cross-validation of a previous study in which the same patterns were found using the Child Behavior Checklist (Vanderlaan et al. in J Sex Res 52:213–19, 2015). We discuss possible developmental pathways between GD and ASD, including a consideration of the principle of equifinality.
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6.

Purpose

The incidence of ventriculoperitoneal (VP) shunt infection accounts for about 5–15 %, but it can rise up to 70 % in specific high-risk subgroups. Antibiotic-impregnated catheters (AICs) have been designed to reduce shunt infections, but reports on their efficacy are discordant, especially in young children. The aim of this study is to assess, for the first time, the efficacy of AICs in newborns and infants at very high risk for shunt infection.

Methods

We reviewed the medical records of newborns and infants treated with a VP shunt for newly diagnosed hydrocephalus. Patients were divided in two groups: Group A was composed by children who received AICs, whereas Group B included children implanted with standard silicone catheters (non-AICs). We compared the shunt infection rate in both groups, and analyzed differences in specific high-risk subgroups (preterm newborns, children with posthemorrhagic or postinfective hydrocephalus, and children with a previous external ventricular drainage).

Results

Forty eight children younger than 1 year old were included in our study. Twenty two patients were implanted with an AIC, whereas 26 patients received a standard silicone catheter. The follow-up was at least 1 year (mean 8?±?3 years). The overall infection rate decreased from 34 % in non-AIC group to 9 % in the AIC group. Moreover, AICs showed to have a protective effect against shunt infections in all the specific high-risk subgroups analyzed.

Conclusions

This study demonstrates for the first time that AICs are effective in reducing VP shunt infection in high-risk pediatric patients younger than 1 year old.
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7.

Background

Atypical sensory processing is a common clinical observation in autism spectrum disorder (ASD). Neural hyperexcitability has been suggested as the cause for sensory hypersensitivity, a frequently reported clinical observation in ASD. We examined visual evoked responses to parametric increases in stimulus contrast in order to model neural responsivity of sensory systems in ASD.

Methods

Thirteen high-functioning individuals with ASD and 12 typically developing (TD) individuals completed a steady-state visual evoked potential study. Stimuli were vertical circular gratings oscillating at 3.76 Hz at varying contrasts (5, 10, 20,…, 90 % contrast, 10 levels). The average spectral power at the stimulus oscillation frequency was calculated for each contrast level.

Results

The magnitude of evoked sensory responses increased at a significantly greater rate and resulted in disproportionately elevated activation with higher contrasts in the ASD group. Approximately 45 % of ASD participants had rates of response increases greater than any TD participant. This alteration was highly associated with parental reports of these participants’ sensory difficulties.

Conclusions

Greater increases in visual responses over contrast manipulation suggest heightened excitability in the sensory cortex in ASD participants. Heightened neural excitability was observed in a substantial portion but not all of the ASD participants. This pattern suggests that individuals with higher excitability may constitute a neurobiologically distinct subgroup requiring individualized treatment interventions.
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8.

Background

Research is yet to investigate whether psychological interventions delivered early after diagnosis can benefit patients with head and neck cancer (HNC).

Purpose

The aim of this study was to investigate the effectiveness of a brief self-regulatory intervention (targeting illness perceptions and coping) at improving HNC patient health-related quality of life (HRQL).

Methods

A pilot randomized controlled trial was conducted, in which 64 patients were assigned to receive three sessions with a health psychologist in addition to standard care or standard care alone. Participants completed questionnaires assessing HRQL, general distress, and illness perceptions at baseline and again 3 and 6 months later.

Results

Compared to the control group, patients who received the intervention had increased treatment control perceptions at 3 months (p = .01), and increased social quality of life at 6 months (p = .01). The intervention was particularly helpful for patients exhibiting distress at baseline.

Conclusion

A brief psychological intervention following HNC diagnosis can improve patient perceptions of treatment and social quality of life over time. Such interventions could be targeted to patients who are distressed in order to confer the greatest benefit.

Trial Registration Number

12614000813684.
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9.

Background

Most work testing links between emotional competencies and health has focused on self-reported and/or trait assessments. However, more objective assessments of skills and knowledge may also predict health relevant outcomes.

Purpose

The current study investigated whether performance-based tests of emotional knowledge and expressive skill predicted symptoms of depression and anxiety, self-reported physical symptoms, perceived health, and a range of immunoregulatory molecules.

Methods

Eighty females aged 18–35 completed self-report assessments before attending a testing session in which they provided blood samples and completed performance-based assessments of expressive skill and emotional knowledge.

Results

Greater expressive skill predicted better self-reported outcomes, but links to immunoregulatory molecules were mixed. Expressive skill for contempt and anger predicted higher, whereas skill for happiness predicted lower, concentrations of immunoregulatory molecules.

Conclusions

These data highlight the need to extend research beyond self-reported emotional competencies and suggest that performance-based skill and knowledge metrics may be associated with health relevant outcomes.
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10.

Background

Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder. Promising initiatives utilizing interdisciplinary characterization of ASD suggest phenotypic subtypes related to specific likely gene-disrupting mutations (LGDMs). However, the role of functionally associated LGDMs in the neural social phenotype is unknown.

Methods

In this study of 26 children with ASD (n?=?13 with an LGDM) and 13 control children, we characterized patterns of mu attenuation and habituation as children watched videos containing social and nonsocial motions during electroencephalography acquisition.

Results

Diagnostic comparisons were consistent with prior work suggesting aberrant mu attenuation in ASD within the upper mu band (10–12 Hz), but typical patterns within the lower mu band (8–10 Hz). Preliminary exploration indicated distinct social sensitization patterns (i.e., increasing mu attenuation for social motion) for children with an LGDM that is primarily expressed during embryonic development. In contrast, children with an LGDM primarily expressed post-embryonic development exhibited stable typical patterns of lower mu attenuation. Neural social indices were associated with social responsiveness, but not cognition.

Conclusions

These findings suggest unique neurophysiological profiles for certain genetic etiologies of ASD, further clarifying possible genetic functional subtypes of ASD and providing insight into mechanisms for targeted treatment approaches.
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11.

Background

Minor physical anomalies (MPAs) are subtle anatomical deviations in one’s appearance and may suggest altered embryogenesis. MPAs have been shown to be more common in neurodevelopmental disorders (NDDs) compared with typical development. Still, further studies are needed on MPAs in NDDs, especially using twins to adjust for confounding familial factors.

Methods

Clinical assessments were conducted on 116 twins (61 NDD, 55 controls) from 51 monozygotic and 7 dizygotic pairs to examine MPAs and their association with DSM-5 defined NDDs. Additionally, the relationship between the number of MPAs within twins by zygosity was investigated.

Results

Within the cohort sample, a specific association was found between MPAs and autism spectrum disorder (ASD) diagnosis (crude odds ratio = 1.29, p = .047; adjusted odds ratios = 1.26–1.33, adjusted p values = .032–.073) and autistic traits (crude β = 3.02, p = .002; adjusted β = 2.28, p = .019), but not NDDs in general or ADHD, nor within-pairs. Identified MPAs in ASD included overweight, hypermobility, pes planus, straight eyebrows, vision impairment, arachnodactyly/long toes, long eyelashes, and microtia. The number of MPAs within all monozygotic pairs was highly correlated (r = .88, p < .001).

Conclusion

MPAs are more frequent in participants with ASD and may be influenced by genetics. The value of MPAs for (early) detection should be further explored, as they might index individuals at increased risk for ASD in particular.
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12.

Background

Most people who quit smoking relapse within a year of quitting. Little is known about what prompts renewed quitting after relapse or how often this results in abstinence.

Purpose

This study seeks to identify rates, efficacy, and predictors of renewed quit attempts after relapse during a 1-year follow-up.

Methods

Primary care patients in a comparative effectiveness trial of smoking cessation pharmacotherapies reported daily smoking every 6–12 weeks for 12 months to determine relapse, renewed quitting, and 12-month abstinence rates.

Results

Of 894 known relapsers, 291 (33 %) renewed quitting for at least 24 h, and 99 (34 %) of these were abstinent at follow-up. The average latency to renewed quitting was 106 days and longer latencies predicted greater success. Renewed quitting was more likely for older, male, less dependent smokers, and later abstinence was predicted by fewer depressive symptoms and longer past abstinence.

Conclusions

Renewed quitting is common and produces meaningful levels of cessation.
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13.

Purpose

The initial symptoms of multiple system atrophy (MSA) and, in particular, early autonomic symptoms, have received less attention than motor symptoms. Whereas pathognomonic motor signs are essential to diagnostic specificity, early symptoms important to recognition of a neurodegenerative disorder may be less apparent or diagnostically ambiguous. This observational study sought to identify the very earliest symptoms in the natural history of MSA.

Methods

Detailed clinical histories focusing on early symptoms were obtained from 30 subjects recently diagnosed with MSA. Historical data were correlated with neurological examinations and laboratory autonomic testing.

Results

Subjects’ mean age was 63.9 years. Ten were classified as having MSA-P and 20 MSA-C. The evaluations occurred 2.9 ± 0.4 months after diagnosis. The first symptom of MSA was autonomic in 22 (73%) and motor in 3 (10%) subjects (p < 0.0001). The most frequent first symptom was erectile failure, which occurred in all men beginning 4.2 ± 2.6 years prior to diagnosis. After erectile failure, postural lightheadness or fatigue following exercise, urinary urgency or hesitancy, and violent dream enactment behavior consistent with REM behavioral sleep disorder were the most frequent initial symptoms. Neither the order of symptom progression, which was highly variable, nor autonomic severity scores differentiated between MSA-P and MSA-C.

Conclusions

The first symptoms of MSA are frequently autonomic and may predate recognition of motor manifestations. Orthostatic hypotension and, in men, erectile failure are among the first symptoms that, when evaluated in the context of associated clinical findings, may facilitate accurate and earlier diagnosis.
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14.

Background

Obesity and poor sleep are highly prevalent among Black women.

Purpose

We examined whether a weight gain prevention intervention improved sleep among Black women.

Methods

We conducted a randomized trial comparing a 12-month weight gain prevention intervention that included self-monitoring through mobile technologies and phone coaching to usual care in community health centers. We measured sleep using the Medical Outcomes Study Sleep Scale at baseline, 12 months, and 18 months. The scale examines quantity of sleep, sleep disturbance, sleep adequacy, daytime somnolence, snoring, shortness of breath, and global sleep problems (sleep problem indices I and II).

Results

Participants (n = 184) were on average 35.4 years and obese (BMI 30.2 kg/m2); 74% made <$30,000/year. At baseline, average sleep duration was 6.4 (1.5) hours. Controlling for weight change and sleep medication, the intervention group reported greater improvements in sleep disturbance [?8.35 (?16.24, ?0.45)] and sleep problems at 12 months: sleep problem index I [?8.35 (?16.24, ?0.45)]; sleep problem index II [?8.35 (?16.24, ?0.45)]. However, these findings did not persist at 18 months.

Conclusions

Preventing weight gain may afford clinical benefit on improving sleep quality.

Trial Registration Number

The trial was registered with the ClinicalTrials.gov database (NCT00938535)
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15.

Object

Ventriculoperitoneal (VP) shunts in infants with posthemorrhagic hydrocephalus (PHH) are prone to failures, with some patients at risk for multiple revisions. The objective of our study is to observe long-term outcomes and identify factors leading to proximal and distal multiple failures.

Methods

We performed a retrospective review of infants with PHH that required VP shunt placement between 1982 and 2014. These patients were monitored clinically and radiographically after VP shunt placement.

Results

A total of 502 surgical procedures (initial shunt insertion and revisions) were performed, with 380 shunt revisions in 102 (84 %) patients. Median shunt survival time was 54 months (0.03–220 months). Shunt survival was significantly affected by the following factors: intraventricular hemorrhage (IVH, grade II–III, 95 months vs. grade IV, 28 months, p = 0.022), birth weight (<1.5 kg, 59 months vs. >1.5 kg, 22 months, p = 0.005), gestational age (>27 weeks, 90 months vs. <27 weeks, 20 months, p < 0.0001), distal vs. proximal revision (133 months vs. 48 months, p = 0.013), obstruction (yes, 78 months vs. no, 28 months, p = 0.007), and infection (no, 75 months vs. yes, 39 months, p = 0.045). Regression analysis revealed that multiple gestation, head circumference (>27 cm), congenital anomalies, infection, and obstruction increased the proximal and distal shunt malfunction.

Conclusion

Long-term outcome of VP shunt placement in infants revealed a relatively high rate of complications requiring shunt revision as late as 30 years after initial placement. Infants with VP shunts should be monitored lifelong of these patients by neurosurgeons.
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16.

Background

Social networks can influence physical activity, but little is known about how best to engineer online and in-person social networks to increase activity.

Purpose

The purpose of this study was to conduct a randomized trial based on the Social Networks for Activity Promotion model to assess the incremental contributions of different procedures for building social networks on objectively measured outcomes.

Methods

Physically inactive adults (n = 308, age, 50.3 (SD = 8.3) years, 38.3 % male, 83.4 % overweight/obese) were randomized to one of three groups. The Promotion group evaluated the effects of weekly emailed tips emphasizing social network interactions for walking (e.g., encouragement, informational support); the Activity group evaluated the incremental effect of adding an evidence-based online fitness walking intervention to the weekly tips; and the Social Networks group evaluated the additional incremental effect of providing access to an online networking site for walking as well as prompting walking/activity across diverse settings. The primary outcome was mean change in accelerometer-measured moderate-to-vigorous physical activity (MVPA), assessed at 3 and 9 months from baseline.

Results

Participants increased their MVPA by 21.0 min/week, 95 % CI [5.9, 36.1], p = .005, at 3 months, and this change was sustained at 9 months, with no between-group differences.

Conclusions

Although the structure of procedures for targeting social networks varied across intervention groups, the functional effect of these procedures on physical activity was similar. Future research should evaluate if more powerful reinforcers improve the effects of social network interventions.

Trial Registration Number

The trial was registered with the ClinicalTrials.gov (NCT01142804).
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17.

Background

Many reports argue that sleep is important for children’s health, learning, and academic performance. The purpose of this longitudinal study was to examine the association between sleep and the development of social competence in infants.

Methods

This study was conducted as part of a Japan Science and Technology Agency (JST) project. Caregivers responded to the Japan Children’s Study Sleep Questionnaire when children were 18 months old. The interactions of caregivers and children were observed when children were 18, 30, and 42 months old, and rated with the Interaction Rating Scale, which is a measure of social competence.

Results

Nocturnal sleep duration of more than 10 h and an earlier bed time than 22:00 were significantly correlated with two trajectory groups (low point and high point transition groups) of children’s social competence at 18, 30, and 42 months. Further, total sleep duration of more than 12.25 h and an earlier bed time than 22:00 were significantly correlated with the trajectory of children’s social competence at 18, 30, and 42 months.

Conclusions

Sleep duration and sleep onset time are important factors in children’s development of social competence.Trial registration The ethics committee of the JST approved this study on March 19, 2001. The registration number is 356-1.
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18.

Purpose

Recalled experiences of parental bonding may be important in the aetiology of perinatal depression. We hypothesized that lower recalled parental bonding would be associated with perinatal depression.

Method

In a cohort study of perinatal depression in Turkey, 677 women were recruited in their third trimester. Parental Bonding Inventory (PBI) scores at baseline were investigated as predictors of depression on the Edinburgh Postnatal Depression Scale (EPDS) at 4, 14 and 21 months after childbirth in mothers without depression at baseline.

Results

Poor parental bonding scores, apart from paternal control and overprotection, were independently associated with antenatal depression. Incident postnatal depression at 4 months was predicted by parental overprotection, at 14 months by parental care and overprotection, and at 21 months by paternal control and overprotection.

Conclusions

Less satisfactory parenting recalled in the antenatal period was an independent predictor of postnatal depression; however, the different bonding subscales varied as predictors according to the timing of the depression assessment after childbirth.
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19.

Background

Gene mutations within the RAS-MAPK signaling cascade result in Noonan syndrome (NS), neurofibromatosis type 1 (NF1), and related disorders. Recent research has documented an increased risk for social difficulties and features of autism spectrum disorder (ASD) among children with these conditions. Despite this emerging evidence, the neuropsychological characteristics associated with social skills deficits are not well understood, particularly for children with NS.

Methods

Parents of children with NS (n?=?39), NF1 (n?=?39), and unaffected siblings (n?=?32) between the ages of 8 and 16 years were administered well-validated caregiver questionnaires assessing their child’s social skills, language abilities, attention-deficit hyperactivity disorder (ADHD) symptoms and anxiety.

Results

With respect to overall social skills, average ratings of children in both clinical groups were similar, and indicated weaker social skills compared to unaffected siblings. Although ratings of social skills were outside of normal limits for more than four in ten children within the clinical groups, most of the deficits were mild/moderate. Fifteen percent of the children with NS and 5% of the children with NF1 were rated as having severe social skills impairment (<???2SD). Independent of diagnosis, having fewer ADHD symptoms or better social-pragmatic language skills was predictive of stronger social skills.

Conclusions

Amidst efforts to support social skill development among children and adolescents with RASopathies, neuropsychological correlates such as social language competence, attention, and behavioral self-regulation could be important targets of intervention.
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20.

Background

Recidivism rates in substance-addicted patients placed in institutions according to §64 of the German legal code are approximately 50%, 3 years after discharge from inpatient treatment. The recidivism rates of patients with premature termination of inpatient treatment who had then been referred back to prison and were finally discharged into the community are unknown.

Research question

Is premature termination of treatment a risk factor for recidivism?

Methods

Patients released from forensic treatment according to § 64 of the German legal code were followed up for violent and non-violent recidivism. Full data were acquired for Baden-Württemberg patients released in 2010 and 2011 with regular vs. premature termination of treatment.

Results

All measures revealed highly significant group differences: 48% of the patients discharged after subsequent prison sentences recidivated within the first year and 73% within 3 years after discharge. Among recidivists, the severity of offences was much higher (odds ratio > 3.8 each). Regularly discharged patients also re-offended to a remarkable extent (50%).

Discussion

Patients serving prison sentences after unsuccessful forensic treatment are a high-risk group for recidivism. Alternative concepts of clinical and legal treatment of this group should be developed.
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