Examining the Duration of Carryover Effect in Patients With Chronic Pain Treated With Spinal Cord Stimulation (EChO Study): An Open, Interventional, Investigator-Initiated, International Multicenter Study.

OBJECTIVES: Spinal cord stimulation (SCS) is a surgical treatment for severe, chronic, neuropathic pain. It is based on one to two lead(s) implanted in the epidural space, stimulating the dorsal column. It has long been assumed that when deactivating SCS, there is a variable interval before the patient perceives the return of the pain, a phenomenon often termed echo or carryover effect. Although the carryover effect has been problematized as a source of error in crossover studies, no experimental investigation of the effect has been published. This open, prospective, international multicenter study aimed to systematically document, quantify, and investigate the carryover effect in SCS. MATERIALS AND METHODS: Eligible patients with a beneficial effect from their SCS treatment were instructed to deactivate their SCS device in a home setting and to reactivate it when their pain returned. The primary outcome was duration of carryover time defined as the time interval from deactivation to reactivation. Central clinical parameters (age, sex, indication for SCS, SCS treatment details, pain score) were registered and correlated with carryover time using nonparametric tests (Mann-Whitney/Kruskal-Wallis) for categorical data and linear regression for continuous data. RESULTS: In total, 158 patients were included in the analyses. A median carryover time of five hours was found (interquartile range 2.5;21 hours). Back pain as primary indication for SCS, high-frequency stimulation, and higher pain score at the time of deactivation were correlated with longer carryover time. CONCLUSIONS: This study confirms the existence of the carryover effect and indicates a remarkably high degree of interindividual variation. The results suggest that the magnitude of carryover may be correlated to the nature of the pain condition and possibly stimulation paradigms. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03386058.

Perinatal outcomes after therapeutic rest in the latent phase of labor: A cohort study.

INTRODUCTION: Therapeutic rest refers to the usage of medication to relieve pain in women in the latent phase of labor. Very few data are available to evaluate the safety and effect of its use. The objectives of this study were to compare perinatal and labor outcomes in women who were seeking hospital care during the latent phase of labor and who were treated either with or without therapeutic rest. MATERIAL AND METHODS: Retrospective cohort study with inclusion of nulliparous singleton pregnant women in the latent phase of labor presenting at the labor ward at Aarhus University Hospital, Denmark from May 13, 2018 to June 1, 2021. We identified two groups: women who were treated with therapeutic rest and women who were not. The primary outcomes were neonatal admission and neonatal resuscitation. Secondary outcomes included use of cardiotocography during labor, nonreactive fetal heart rate, meconium-stained amniotic fluid, pediatric delivery room assistance, umbilical cord arterial pH and standard base excess, Apgar score at 5 minutes, interventions during labor and mode of delivery. RESULTS: In our sample of 800 women in the latent phase of labor, 414 women (52%) were treated with therapeutic rest and 386 women (48%) were not. The most frequently used (n = 206) medication for therapeutic rest was a combination of paracetamol, triazolam and codeine. We found no significant difference in neonatal admission (9.2% vs 6.5%, adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 0.4-3.1) or neonatal resuscitation (2.4% vs 3.1%, aOR 0.7, 95% CI 0.1-4.0) between women treated with or without therapeutic rest. There were no differences between the two groups in other perinatal adverse outcomes, interventions during labor or mode of delivery. CONCLUSIONS: This study found no significant association between therapeutic rest and neonatal admission or resuscitation. Our findings indicate that therapeutic rest is a safe method for managing the latent phase of labor concerning neonatal health and does not increase the risk of labor complications.

Management of child maltreatment suspicions in general practice: a mixed methods study.

BACKGROUND: Maltreated children have many long-term consequences throughout their lives, but often maltreated children are not recognised in time by professionals. General practice could be central to the early recognition of child maltreatment due to the long-term relationship with families. OBJECTIVE: How do general practitioners (GPs) and practice nurses (PNs) deal with suspected maltreatment in children below 18 years of age, and which factors influence them to report cases to social authorities. DESIGN AND SETTING: A mixed methods study set in general practice in Denmark. METHOD AND SUBJECTS: We combined data from a nationwide questionnaire with observations from five clinics and 20 interviews with GPs and PNs. We explored our data using the concept of uncertainty as a driver that shapes action and decision-making in general practice. RESULTS: Most GPs (94%) said they would discuss cases of suspected child maltreatment with social services, but in many cases they would prefer to discuss their suspicions with a colleague first (83%) - most likely where there are no clear-cut signs. The qualitative data added nuance to these findings by highlighting the difficulty of communicating across sectors, the importance of maintaining a connection with the child's family, and practicing watchful waiting. CONCLUSION: General practice has an opportunity to act early in cases of suspected child maltreatment if uncertainty is accepted as a critical part of the process of reaching a diagnosis. Communication across sectors is key, as is support for GPs with suspicions and for families in need of help.Key pointsGPs are often thought to underreport child maltreatment but despite low levels of reporting, this does not mean they ignore it.Building on the connection with the family, making follow appointments, and discussing suspicions with colleagues are typical of how GPs manage suspicions of child abuse.Accepting uncertainty as a condition of raising the alarm could help GPs to act quickly to support children at risk of abuse.

Burst Spinal Cord Stimulation in Pregnancy: First Clinical Experiences.

OBJECTIVES: Spinal cord stimulation (SCS) is a treatment for chronic neuropathic pain. It is based on the delivery of electric impulses to the spinal cord, traditionally in a regular square-wave pattern ("tonic" stimulation) and, more recently, in a rhythmic train-of-five "BurstDR" pattern. The safety of active SCS therapy in pregnancy is not established, and recommendations are based on limited casuistic evidence. We present in this study clinical data on a case series of six women treated with burst SCS during pregnancy. In addition, we present the ultrasonographic flow measurements of fetal and uteroplacental blood flow in a pregnant patient. MATERIALS AND METHODS: Patients were included if they had been implanted with a full SCS system at Aarhus University Hospital, Denmark, between 2006 and 2020 and received active burst SCS stimulation during a pregnancy. Telephone interviews were conducted, including details on SCS therapy, medication, pregnancy course and outcome, and health status of the offspring. In one patient, the uteroplacental and fetal blood flow was assessed in gestational week 29 by Doppler flow measurements performed during both ON and OFF phases of the SCS system. RESULTS: Six patients were included with a total of 11 pregnancies. Three pregnancies ended in miscarriages, all in the same patient who had preexisting significant risk factors for miscarriage. Eight resulted in a live-born child with normal birth weight for gestational age; seven were born at term, and one was born late preterm, in gestational week 36. Ultrasonographic Doppler flow, measured in one patient, was normal and did not reveal any immediate changes between burst SCS ON and OFF. Seven children were reported healthy with normal neurodevelopment and one physically healthy but with developmental delays. CONCLUSIONS: The data presented in this study add to the accumulating evidence of the safety of SCS in pregnancy.

Early-term elective Caesarean sections did not increase the risk of behavioural problems at six to eight years of age.

AIM: Our aim was to explore the under-researched associations between an elective Caesarean section (C-section) at early-term or full-term gestation and behaviour at 6-8 years of age. METHODS: We identified 1220 eligible children born by elective C-sections at Danish hospital from 2009 to 2011. Their mothers were randomised to elective C-sections at either 38+3 (early-term) or 39+3 (full-term) weeks of gestation. From December 2017 to August 2018, the parents completed the Strengths and Difficulties Questionnaire. The results were adjusted for maternal education, parity and the child's sex. RESULTS: Of the 574 (45%) children followed up, 288 were delivered early-term and 286 were delivered full-term. The groups had similar baseline characteristics. There were no differences in the total difficulties score, subscale scores or the risk of being classified as having a possible or probable psychiatric disorder. Early-term boys had a lower risk of being classified as having a possible or probable psychiatric disorder and early-term girls had higher risk, but the results were not statistically significant. CONCLUSION: We found no difference in behaviour at 6-8 years of age between children born by elective C-section at early- versus full-term gestation.

Seasonal variation in the hypertensive disorders of pregnancy in Denmark.

INTRODUCTION: Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of morbidity and mortality for both mother and fetus. It has been proposed that vitamin D affects a number of biological processes involved in the pathogenesis of hypertensive disorders of pregnancy. Therefore, a seasonal variation in the risk of these disorders might be expected in areas such as Denmark with marked seasonal variation in sunlight exposure. In this study, we aimed to evaluate the existence of this association. MATERIAL AND METHODS: We used information from a cohort of 50 665 previously healthy, nulliparous women with singleton pregnancies. All women gave birth between 1989 and 2010 at Aarhus University Hospital, Denmark. Logistic regression analyses combined with the cubic spline method were used to estimate the seasonal variation for each outcome: gestational hypertension and preeclampsia, after adjusting for calendar time. RESULTS: Of the 50 665 women included, 8.5% were diagnosed with a hypertensive disorder of pregnancy. The overall tendency was towards increasing risk when conceiving during spring and early summer, peaking midsummer, and subsequently decreasing steadily during late summer and fall to reach the nadir by winter. Seasonal variation was found for; gestational hypertension (P = .01); preeclampsia (P = .001) and early-onset preeclampsia (P = .014). CONCLUSIONS: We found a seasonal variation in the risk of the hypertensive disorders of pregnancy in a large cohort of Danish nulliparous women. The highest risk was seen in women with the estimated date of conception in June and August, that is, during summer. Seasonal variation in vitamin D status may explain this association.

Long-term cognition and behavior in children born at early term gestation: A systematic review.

INTRODUCTION: Recent recommendations characterize deliveries at 37+0  weeks through 38+6  weeks as early term. We aimed to review the literature systematically on long-term cognition, school performance and behavior in children born early term (37+0 to 38+6 weeks) compared with full term (39+0  to 40+6 weeks). MATERIAL AND METHODS: The review was performed according to the PRISMA Statement. The final literature search was performed on 31 January 2019. We located studies in PubMed, Embase, CINAHL and Cochrane Library. Eligible studies were randomized controlled trials, cohort studies and case-control studies, with outcome assessment performed at 2-19 years. We collected information using a structured data form and evaluated study quality using the Newcastle-Ottawa Scale (NOS). RESULTS: We included 42 observational studies published between 2006 and 2018. No restriction on year of publication was made. The mean NOS score was 5.8 with a range from 3 to 9. Compared with children born full term, children born early term had a lower intelligence score in early adulthood and up to some 30% increased risk of attention-deficit/hyperactivity disorder. Furthermore, we found some 10%-40% increased risk of cognitive problems, some 25% higher risk of language impairments and another 8%-75% with poorer overall school performance. No meta-analysis was conducted due to heterogeneity in the outcome measures. Only 10 studies presented subgroup analyses in spontaneous deliveries or adjusted for type of labor onset/induction. CONCLUSIONS: Children born early term are at increased risk of cognitive deficits, poorer school performance and behavioral problems compared with children born full term.

Neonatal morbidity after spontaneous labor onset prior to intended cesarean delivery at term: a cohort study.

INTRODUCTION: We aimed to investigate if labor onset before planned cesarean delivery (CD) affects the risk of neonatal admission, respiratory distress, or neonatal infectious morbidity. MATERIAL AND METHODS: Our cohort included singleton term pregnant women with intended CD who delivered at Aarhus University Hospital from 1990 to 2012. Two groups of women were identified: women with intended CD performed before labor (nonlabor CD) and women with intended CD performed after spontaneous labor onset (labor-onset CD); in both groups there was no other maternal or fetal medical indication for an immediate CD or for early-term CD scheduling. Data were stratified in early-term (37-38 weeks) and full-term (39-40 weeks) deliveries. The main outcome measures were neonatal admission, respiratory distress and neonatal infectious morbidity. RESULTS: Among 103 919 live births, 5071 deliveries were nonlabor CDs and 731 were labor-onset CDs. Compared to nonlabor CD, labor-onset CD was associated with similar risks of neonatal admission and respiratory distress, both at early and full term, but with a two- to three-fold increased risk of newborn septicemia or antibiotic treatment at early term. Labor onset at early term was associated with a lower risk of maternal blood loss of more than 500 mL, but with a higher risk of postoperative antibiotic treatment and endometritis. CONCLUSIONS: Labor onset before planned CD was not associated with a decrease in neonatal respiratory morbidity, but may be associated with increased risks of neonatal infection.

Developmental Coordination Disorder in Children with a History of Infantile Colic.

OBJECTIVE: To investigate whether children with a history of infantile colic showed impaired motor development at age 7 years compared with unaffected peers. STUDY DESIGN: We studied 27,940 children from the Danish National Birth Cohort (1997-2002), including 1879 (6.8%) with a history of infantile colic. Infantile colic was defined according to the modified Wessel criteria as crying for more than 3 hours per day and more than 3 days per week. We compared the parental Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07) scores in children with and without infantile colic after adjustment for intrauterine exposures, feeding type, parity, maternal age, socioeconomic status, Apgar score, gestational age, and birth weight. RESULTS: Children with a history of infantile colic had an elevated risk of scoring above the predefined cutoff limit of possible or suspected developmental coordination disorder (OR, 1.3; 95% CI, 1.0-1.7; P = .034). The mean total DCDQ'07 score was -0.4 point (95% CI, -0.8 to 0) lower in children with a history of infantile colic. Moreover, they were at higher risk for a low total score (OR for a 10-point decrease, 1.1; 95% CI, 1.0-1.1; P = .006) and a low general coordination score (OR, 1.3; 95% CI, 1.1-1.5, P = .000) in the DCDQ'07. All associations appeared to be stronger among boys, but no statistically significant effect measure modification between infantile colic and sex was found. CONCLUSION: We found no evidence of a strong association between infantile colic and developmental coordination disorder in this large Danish cohort.

Gestational age, small for gestational age, and infantile colic.

BACKGROUND: Preterm and growth restricted infants may have developmental delays and deviations from normal organ function related to the gastrointestinal tract and the central nervous system. Since both organ systems are hypothesised to be involved in the pathogenesis of infantile colic, a condition characterised by excessive crying during the first months of life, impaired fetal growth and preterm birth may be risk factors for infantile colic. METHODS: A total of 62,761 liveborn singletons from the Danish National Birth Cohort (1996 to 2002) were studied. Infantile colic was defined according to Wessel's modified criteria based on maternal interview conducted at 6 months post-partum. RESULTS: A total of 2605 (4.2%) infants were born preterm, 54,441 (86.7%) at term, and 5715 (9.1%) post-term. A total of 4964 (7.9%) infants fulfilled Wessel's modified criteria for infantile colic. The risk for infantile colic increased with decreasing gestational age after adjustment for covariates. The highest odds [odds ratio (95% confidence interval)] was observed for infants born before 32 completed gestational weeks (1.5 [95% CI 1.0, 2.2], reference: 40 gestational weeks). Small for gestational age infants (birthweight below 10th percentile) had an increased odds of infantile colic (1.2 [95% CI 1.1, 1.3]) in all gestational age groups. CONCLUSIONS: We observed an increased risk of infantile colic in preterm and small for gestational age infants in a large cohort. Our results suggest that the aetiology of infantile colic may be found in the prenatal, perinatal, and neonatal period.

The Aarhus Neuromodulation Database.

OBJECTIVES: €‚ Spinal cord stimulation (SCS) is increasingly gaining widespread use as a treatment for chronic pain. A widely used electronic registry could play a pivotal role in improving this complex and cost-€intensive treatment. We aimed to construct a comprehensive, universally available data base for SCS. MATERIALS AND METHODS: €‚ The design considerations behind a new online data base for SCS are presented; basic structure, technical issues, research applications, and future perspectives are described. RESULTS: €‚ The Aarhus Neuromodulation Database covers core SCS treatment parameters, including procedure-€related details and complications, and features recording of key success parameters such as pain intensity, work status, and quality of life. It combines easy access to patient information with exhaustive data extraction options, and it can readily be adapted and expanded to suit different needs, including other neuromodulation treatment modalities. CONCLUSIONS: €‚ We believe that the data base described in this article offers a powerful and versatile data collection tool suited for both clinicians and researchers in the field. The basic data base structure is immediately available on a no€-cost basis, and we invite our colleagues to make use of the data base as part of the efforts to further the field of neuromodulation.

Virtual Reality Treatment of Severe Neuropathic Pain in an Adolescent Child: A Case Report.

We describe virtual reality (VR) used as an effective intervention to treat severe chronic neuropathic pain in an otherwise healthy adolescent boy. The patient presented with severe pain and allodynia in the right foot after calcaneus extension surgery. Multiple medical and psychological interventions were unsuccessful over 3 years, with the pain leading the patient to drop out of school. VR gaming intervention provided the patient with significant pain relief and substantial improvement in functionality. This case report details the VR intervention and its effect on the patient's severe, medically refractory pain syndrome.

Suspicion of child maltreatment: Knowledge and experiences with mandatory reports to social services among general practitioners in Denmark in 2019-20.

BACKGROUND: Child maltreatment has many consequences through the lifespan. The general practitioners (GPs) are in longitudinal contact with the family and can play an important role in identifying children in danger and reporting to the social services. OBJECTIVE: To explore how GPs manage suspicions of child maltreatment and to investigate potential demographic and geographic differences in reporting practices among Danish GPs. PARTICIPANTS AND SETTING: All registered GPs in Denmark retrieved from Medcom, a state-financed non-profit organization. METHODS: We mailed a questionnaire to all registered GPs with demographics, experiences, knowledge, and attitudes in the context of child maltreatment. RESULTS: We received 1252 completed questionnaires (response rate: 38 %). Most of the participants had suspected child maltreatment during their professional life (90 %) and had made a mandatory report (85 %). More than half had received feedback after the report (56 %) and said that their report led to action (56 %). Most GPs reported feeling confident in dealing with child maltreatment (79 %) and being willing to get involved in case of suspicion (8.9 on a 0-10 scale). We observed no geographical differences in reporting neither across the Danish regions nor among rural and urban practices, but GPs working in single practices made fewer reports to the social services. CONCLUSIONS: Participant GPs in this study are aware of their role in child protection, have experiences with mandatory reports, and are willing to get involved. Possible areas for attention include collaboration and support between different settings, especially between GP practice, hospitals, justice sector, and social services.

Lethal abusive head trauma in infancy in Denmark from 2000 to 2011.

INTRODUCTION: We aimed to estimate the incidence of lethal abusive head trauma (AHT) in infancy in Denmark from 2000 through 2011 and to describe autopsy findings and information from police reports on lethal AHT cases. METHODS: This was a nationwide retrospective study. We identified AHT cases in the National Cause of Death Register (CODR) and in forensic archives and compared data from the two sources. Moreover, we collected data on medical history, witness statements and conviction reports from police files and the Director of Public Prosecutions. RESULTS: We identified eight cases of lethal infant AHT (incidence: 1.04 per 100,000 person years). Three AHT cases from autopsy reports were not registered correctly in the CODR. The median age of the victims was 46.5 days. They all had recent subdural and/or subarachnoid haemorrhage. We also found a high prevalence of retinal haemorrhage and fractures. Seven perpetrators were identified, all male relatives, and all were convicted. We moreover identified a surprisingly large number of infants with unspecific cause of death and missing information on whether an autopsy had been performed in the CODR (n = 56). CONCLUSIONS: The incidence of lethal infant AHT found in this study is lower than findings from most other countries. Data from the CODR are inadequate for identifying all lethal AHTs. Further studies including non-fatal cases of AHT are needed to determine the real incidence of AHT in Denmark. FUNDING: none. TRIAL REGISTRATION: not relevant.

Vitamin D and the risk of dystocia: A case-control study.

BACKGROUND: Dystocia is one of the most common causes of cesarean section in nulliparous women. Studies have described the presence of vitamin D receptors in the myometrium, but it is still unclear whether vitamin D affects the contractility of the smooth muscles. We therefore aimed to determine the association between the vitamin D serum level at labor and the risk of dystocia. METHOD: We conducted a case-control study between January 2012 and June 2017. Cases were primiparous women, with spontaneous onset of labor, who gave birth by cesarean section due to dystocia. Controls were primiparous women with a spontaneous vaginal delivery. We included 60 women (30 cases and 30 controls) in the analysis. The differences between cases and controls were assessed using chi-squared test for categorical variables and two-sample t-test or unequal t-test for continuous variables, as appropriate, after evaluation of whether they followed the normal distributions. RESULTS: The mean serum 25-hydroxyvitamin D concentrations were 53.1nmol/l (95%CI; 45.2 to 60.9) among cases and 69.9nmol/l (95%CI; 57.5 to 82.4) among controls (P = 0.02). The mean plasma parathyroid hormone levels were 2.25 pmol/l and 2.38, respectively (P = 0.57). Even though 78% of all women reported taking a minimum of 10µg/day of vitamin D throughout pregnancy, 43% had vitamin D insufficiency, defined as serum 25-hydroxyvitamin D levels below 50nmol/l. CONCLUSIONS: In a Danish group of women having a cesarean section due to dystocia, we found decreased vitamin D levels.

Seasonal variation of dystocia in a large Danish cohort.

BACKGROUND: Dystocia is one of the most frequent causes of cesarean delivery in nulliparous women. Despite this, its causes are largely unknown. Vitamin D receptor (VDR) has been found in the myometrium. Thus, it is possible that vitamin D affects the contractility of the myometrium and may be involved in the pathogenesis of dystocia. Seasonal variation of dystocia in areas with distinct seasonal variation in sunlight exposure, like Denmark, could imply that vitamin D may play a role. This study examined whether there was seasonal variation in the incidence of dystocia in a Danish population. METHOD: We used information from a cohort of 34,261 nulliparous women with singleton pregnancies, spontaneous onset of labor between 37 and 42 completed gestational weeks, and vertex fetal presentation. All women gave birth between 1992 and 2010 at the Department of Obstetrics and Gynecology, Aarhus University Hospital, Skejby. Logistic regression combined with cubic spline was used to estimate the seasonal variation for each outcome after adjusting for calendar time. RESULTS: No evidence for seasonal variation was found for any of the outcomes: acute cesarean delivery due to dystocia (p = 0.44); instrumental vaginal delivery due to dystocia (p = 0.69); oxytocin augmentation due to dystocia (p = 0.46); and overall dystocia (p = 0.91). CONCLUSION: No seasonal variation in the incidence of dystocia was observed in a large cohort of Danish women. This may reflect no association between vitamin D and dystocia, or alternatively that other factors with seasonal variation and influence on the occurrence of dystocia attenuate such an association.

Nicotine replacement therapy during pregnancy and infantile colic in the offspring.

OBJECTIVE: To investigate the associations between use of nicotine replacement therapy (NRT) and smoking during pregnancy and infantile colic in the offspring. METHODS: We used data from maternal interviews (from pregnancy and at 6 months post partum) from the Danish National Birth Cohort (1996-2002). We included 63 128 live-born singletons with complete information on nicotine exposure during pregnancy and infantile colic symptoms as recorded at 6 months of age. RESULTS: A total of 46 660 infants (73.9%) were unexposed to nicotine during pregnancy; 207 (0.3%) were exposed to NRT, 15 016 (23.8%) were exposed to smoking, and 1245 (2.0%) to both. A total of 4974 (7.9%) infants fulfilled Wessel's modified criteria for infantile colic. Prenatal nicotine exposure was associated with elevated risk for infantile colic in the offspring. Compared with the unexposed, NRT users had an adjusted odds ratio (OR) (95% confidence interval) of 1.6 (1.0-2.5; P = .03), smokers had OR = 1.3 (1.2-1.4), and women who both smoked and used NRT had OR = 1.6 (1.3-1.9). Partners' smoking was not associated with infantile colic after adjustment for maternal smoking. CONCLUSIONS: We corroborated the association between smoking and infantile colic after adjustment for several possible confounders in a large cohort study. Moreover, we found that infants exposed to NRT prenatally had an increased risk for infantile colic of the same magnitude as those exposed to tobacco smoke. Thus, nicotine may play a role in the pathogenesis of infantile colic.