Long-Term Follow-Up Results of Mechanical Wrist Traction as Non-Invasive Treatment for Carpal Tunnel Syndrome.

Background: For patients with carpal tunnel syndrome (CTS), the only long-term effective treatment option is carpal tunnel release surgery. Up to one-third report recurrent symptoms, and 12% needs repeated surgery. This study aimed to evaluate the long-term effects of mechanical traction as a non-invasive treatment option for CTS compared to care as usual. Methods: Patients with electrodiagnostically confirmed CTS [N = 181; mean age, 58.1 (13.0) years; 67% women] were recruited from an outpatient neurology clinic in the Netherlands. Patients completed baseline questionnaires and randomized to the intervention group (12 treatments with mechanical traction, twice a week for 6 weeks) or care as usual. The primary clinical outcome measure was surgery during the 12-month follow-up. Secondly, we assessed symptom severity with the Boston Carpal Tunnel Questionnaire (BCTQ) at baseline and at the 12-month follow-up. Changes in CTS symptom severity between baseline and the 12-month follow-up were analyzed between groups using t-tests and a multiple linear regression analyses, adjusting for duration of complaints, age, gender, and symptom severity at baseline. Results: At the 12-month follow-up, 35 of 94 (37%) patients in the intervention group had surgery, compared to 38 of 87 (44%) in the care-as-usual group ( χ 1 2 = 0.78, p = 0.377). Symptom severity and functional status scores did not significantly differ between the intervention (n = 81) and care-as-usual group (n = 55) at follow-up. For patients who did not have surgery, BCTQ scores decreased significantly more from baseline to the 12-month follow-up in the intervention group (n = 53) compared to patients in the care-as-usual group (n = 25). For patients who did not have surgery, belonging to the intervention group and a higher BCTQ score at baseline were related to a greater decrease in BCTQ scores from baseline to the 12-month follow-up, as well as symptom severity and functional status. Conclusions: Mechanical traction is effective in reducing symptom severity compared to current conservative treatment options in standard care and can therefore benefit the large number of patients that prefer conservative treatment for CTS. Clinical Trial Registration: Clinical Trials NL44692.008.13. Registered 19 September 2013, https://clinicaltrials.gov/ct2/show/NCT01949493.

The Brabant study: design of a large prospective perinatal cohort study among pregnant women investigating obstetric outcome from a biopsychosocial perspective.

BACKGROUND: Pregnancy is characterised by many biological and psychosocial changes. Adequate maternal thyroid function is important for the developing fetus throughout gestation. Latent class analyses recently showed three different patterns of change in thyroid function throughout pregnancy with different associations with obstetric outcome. Maternal distress during the pregnancy (anxiety and depression) negatively affects obstetric outcome. Pregnancy distress in turn may be affected by personality traits and attachment styles. Moreover, during the pregnancy, substantial social changes occur in the partner relationship and work experience. The aim of the Brabant study is to investigate the association between thyroid function trajectories and obstetric outcomes. Moreover, within the Brabant study, we will investigate how different trajectories of pregnancy distress are related to obstetric outcome, and the role of personality in this association. We will evaluate the possible role of maternal distress and attachment style on maternal-fetal bonding. Finally, we will study social changes in the perinatal period regarding partner relationship and well-being and performance at work. METHODS AND ANALYSIS: The Brabant study is a longitudinal, prospective cohort study of an anticipated 4000 pregnant women. Women will be recruited at 8-10 weeks gestation among community midwife practices in South-East Brabant in the Netherlands. Thyroid function parameters (TSH and fT4), thyroid peroxidase antibody and human chorionic gonadotrophin will be assessed at 12, 20 and 28 weeks gestation. Moreover, at these three time points women will fill out questionnaires assessing demographic and obstetric features, life style habits and psychological and social variables, such as depressive symptoms, personality, partner relationship quality and burnout. Data from the obstetric records will also be collected. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethical Committee of the Máxima Medical Center Veldhoven. Results will be submitted to peer-reviewed journals in the relevant fields and presented on national and international conferences.

Association of maternal thyroid function with birthweight: a systematic review and individual-participant data meta-analysis.

BACKGROUND: Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight. METHODS: In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496. FINDINGS: We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT4]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT4 with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (pinteraction=0·10). Each 1 SD increase in FT4 concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second. INTERPRETATION: Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT4 (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy. FUNDING: Netherlands Organization for Scientific Research (grant 401.16.020).

Online mindfulness-based intervention for women with pregnancy distress: design of a randomized controlled trial.

BACKGROUND: Psychological distress during pregnancy is common: up to 20% of the childbearing women experience symptoms of depression and anxiety. Apart from the adverse effects on the woman herself, pregnancy distress can negatively affect pregnancy outcomes, infant health, postpartum mother-child interaction and child development. Therefore, the development of interventions that reduce pregnancy distress is very important. Mindfulness-based interventions (MBIs) show promising positive effects on pregnancy distress, but there is a need for randomized controlled trials with sufficient power. Trials on online MBIs, which are readily accessible and not expensive, also show positive effects on stress reduction in non-pregnant populations. Moreover, specific working mechanisms of MBIs remain unclear. The aim of the current study is to test the effectiveness of an online MBI in pregnant women with pregnancy distress, as well as exploring potential working mechanisms. METHODS: The current study is a randomized controlled trial with repeated measures. Consenting women with elevated levels of pregnancy distress will be randomized into an intervention group (MBI) or control group (care as usual) around 12 weeks of pregnancy, with an intended sample size of 103 women in each group. The primary outcome, pregnancy distress, will be assessed via questionnaires at baseline, halfway through the intervention and post intervention in both intervention and control group, and after 8 weeks follow-up in the intervention group. Secondary outcomes are mindfulness skills, rumination and self-compassion, which are also seen as potential working mechanisms, and will be assessed via questionnaires before intervention, halfway through the intervention, post intervention and after 8 weeks follow-up in the intervention group. Tertiary outcome variables are obstetric data and will be collected from the obstetric records for both intervention and control group. Analyses will be based on the intention-to-treat principle. Multilevel regression models for repeated measures (mixed models) will be used to evaluate changes in primary and secondary outcome variables. Tertiary outcomes will be compared between groups using independent t-tests and Chi Square analyses. DISCUSSION: The trial is expected to increase knowledge about the effectiveness of online MBIs during pregnancy in women with pregnancy distress and to evaluate potential working mechanisms. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03917745, registered on 4 March 2019. Protocol Version 3.0., 20 February 2020.

Maternal cognitive function during pregnancy in relation to hypo- and hyperthyroxinemia.

OBJECTIVE: To assess a possible relationship between maternal cognitive dysfunction during pregnancy and hypothyroxinemia, adjusted for major confounders. BACKGROUND: Thyroid dysfunction in general is associated with cognitive dysfunction. Cognitive dysfunction is common during pregnancy. DESIGN: Prospective follow-up study from 12 to 32 weeks of pregnancy. PARTICIPANTS: 2082 healthy pregnant women. MEASUREMENTS: Cognitive function, depression and sleeping problems were assessed by self-report questionnaires at 12, 22 and 32 weeks of gestation, higher scores reflecting more symptoms. FT4, TSH and TPO-Ab were assessed at 12 weeks of gestation. DEFINITIONS: healthy (euthyroxinemia) control group: FT4 within 10-90th percentiles, without elevated TPO-Ab titres and TSH within first trimester-specific reference range (0.23-4.0 mU/L). Hypothyroxinemia: FT4 <2.5th percentile with TSH within first trimester-specific reference range. Poor cognitive function: a score >1 SD > mean on the cognitive function scale. RESULTS: A total of 54 women showed hypothyroxinemia and 1476 women had euthyroxinemia. At 12 weeks, multiple logistic regression showed that poor cognitive function was independently related to hypothyroxinemia: OR: 2.9 (95% CI: 1.6-5.4), adjusted for depression (OR: 3.1; 95% CI: 2.7-4.6) and sleeping problems (OR: 2.8, 95% CI: 1.9-3.9). TPO-Ab + women with hypothyroxinemia had the highest levels of cognitive dysfunction. Other cut-offs of hypothyroxinemia (<5th or <10th percentile with normal TSH) showed similar results. GLM-ANOVA showed that throughout pregnancy women with hypothyroxinemia at 12 weeks had significantly higher cognitive dysfunction scores compared with the healthy controls: F = 12.1, P = .001. CONCLUSIONS: Women with hypothyroxinemia during early gestation are at risk for poor cognitive function throughout gestation, adjusted for depression and sleeping problems.

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Mechanical wrist traction as a non-invasive treatment for carpal tunnel syndrome: a randomized controlled trial.

BACKGROUND: Carpal tunnel syndrome (CTS) is a common, compressive nerve-entrapment disorder with symptoms of numbness, paresthesia, and pain. Carpal tunnel release surgery is the only known long-term effective treatment. However, surgery is invasive and up to 30% of patients report recurrence or persistence of symptoms or suffer from post-surgical complications. A promising non-surgical treatment for CTS is mechanical wrist traction. The purpose of this study was to evaluate clinical outcomes following mechanical traction in patients with CTS compared to care as usual. METHODS: Adult patients (N = 181, mean age 58.1 (13.0) years, 67% women) with electrodiagnostically confirmed CTS were recruited from an outpatient neurology clinic in the Netherlands between October 2013 and April 2015. After baseline assessments, patients were randomized to either the intervention group (12 treatments with mechanical traction, twice a week for a period of 6 weeks) or "care as usual". The main clinical outcome measure was surgery during 6 months' follow-up. In addition, symptom severity was measured using the Boston Carpal Tunnel Questionnaire (BCTQ) at baseline, 3, and 6 months' follow-up. Baseline characteristics and severity of CTS symptoms at follow-up were compared between the intervention and care-as-usual groups using a t test and χ 2 tests. Time to event (surgery) between the groups was analyzed using Kaplan-Meier survival analysis and Cox proportional hazards analysis. RESULTS: The intervention group had fewer surgeries (28%) compared to the care-as-usual group (43%) during follow-up (χ21 = 4.40, p = .036). Analyses of the survival curves revealed a statistically significant difference between the groups over time (log-rank test χ 21 = 6.94, p = .008). At 6 months' follow-up, symptom severity and functional status scores had significantly decreased from baseline in both groups (p < .001) and the improvements did not differ between the two groups. CONCLUSIONS: Mechanical traction is associated with fewer surgical interventions compared to care as usual in CTS patients. Reductions in patient-reported symptoms at 6 months' follow-up was similar in both groups. The long-term effects of mechanical traction require further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NL44692.008.13 . Registered on 19 September 2013.

The HAPPY study (Holistic Approach to Pregnancy and the first Postpartum Year): design of a large prospective cohort study.

BACKGROUND: The HAPPY study is a large prospective longitudinal cohort study in which pregnant women (N ≈ 2,500) are followed during the entire pregnancy and the whole first year postpartum. The study collects a substantial amount of psychological and physiological data investigating all kinds of determinants that might interfere with general well-being during pregnancy and postpartum, with special attention to the effect of maternal mood, pregnancy-related somatic symptoms (including nausea and vomiting (NVP) and carpal tunnel syndrome (CTS) symptoms), thyroid function, and human chorionic gonadotropin (HCG) on pregnancy outcome of mother and foetus. METHODS/DESIGN: During pregnancy, participants receive questionnaires at 12, 22 and 32 weeks of gestation. Apart from a previous obstetric history, demographic features, distress symptoms, and pregnancy-related somatic symptoms are assessed. Furthermore, obstetrical data of the obstetric record form and ultrasound data are collected during pregnancy. At 12 and 30 weeks, thyroid function is assessed by blood analysis of thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibodies (TPO-Ab), as well as HCG. Also, depression is assessed with special focus on the two key symptoms: depressed mood and anhedonia. After childbirth, cord blood, neonatal heel screening results and all obstetrical data with regard to start of labour, mode of delivery and complications are collected. Moreover, mothers receive questionnaires at one week, six weeks, four, eight, and twelve months postpartum, to investigate recovery after pregnancy and delivery, including postpartum mood changes, emotional distress, feeding and development of the newborn. DISCUSSION: The key strength of this large prospective cohort study is the holistic (multifactorial) approach on perinatal well-being combined with a longitudinal design with measurements during all trimesters of pregnancy and the whole first year postpartum, taking into account two physiological possible markers of complaints and symptoms throughout gestation: thyroid function and HCG. The HAPPY study is among the first to investigate within one design physiological and psychological aspects of NVP and CTS symptoms during pregnancy. Finally, the concept of anhedonia and depressed mood as two distinct aspects of depression and its possible relation on obstetric outcome, breastfeeding, and postpartum well-being will be studied.

Effectiveness of mechanical traction as a non-surgical treatment for carpal tunnel syndrome compared to care as usual: study protocol for a randomized controlled trial.

BACKGROUND: Carpal tunnel syndrome (CTS) is a common condition (prevalence of 4%) where the median nerve is compressed within the carpal tunnel resulting in numbness, tingling, and pain in the hand. Current non-surgical treatment options (oral medication, corticosteroid injections, splinting, exercise, and mobilization) show limited effects, especially in the long-term. Carpal tunnel release (CTR) surgery is effective in 70 to 75% of patients, but is relatively invasive and can be accompanied by complications. In an observational study, mechanical traction proved to be effective in up to 70% of patients directly after treatment and in 60% after two years follow-up. This randomized controlled trial (RCT) will examine the effectiveness of mechanical traction compared to care as usual in CTS. METHODS/DESIGN: Patients diagnosed with CTS will be recruited from an outpatient neurology clinic and randomly assigned to the intervention group (mechanical traction) or the control group (care as usual). Participants in the intervention group will receive 12 treatments with mechanical traction during six consecutive weeks. Primary outcome is symptom severity and functional status, which are measured with the Boston Carpel Tunnel Questionnaire (BCTQ). Secondary outcomes are quality of life (WHOQOL-BREF), health related resource utilization, and absenteeism from work. Outcomes will be assessed at baseline, and at 3, 6, and 12 months after inclusion. Linear mixed effect models will be used to determine the change from baseline at 12 months on the BCTQ, WHOQOL-BREF, absenteeism from work and health related resource utilization. The baseline measurement, change from baseline at three and six months, as well as duration of symptoms until inclusion, age, gender, and co-morbidity will be included as covariates The Pearson's correlation coefficient will be generated to assess the correlation between depression and anxiety and treatment outcome. DISCUSSION: Since current non-surgical treatment options are not effective long-term and CTR is relatively invasive, there is a need for an effective and non-invasive treatment option. Mechanical traction is a safe treatment option that may provide a good alternative for the usual care. Considering the prevalence of CTS, the study is of great clinical value to a large patient population. TRIAL REGISTRATION: Clinical Trials NL44692.008.13 (registered on 19 September 2013).