Dataset Information

Identifying potential treatment effect modifiers of the effectiveness of chiropractic care to infants with colic through prespecified secondary analyses of a randomised controlled trial.

ABSTRACT:

Background

A recent trial identified large variation in effect of chiropractic care for infantile colic. Thus, identification of possible effect modifiers could potentially enhance the clinical reasoning to select infants with excessive crying for chiropractic care. Therefore, the aim of this study is to identify potential treatment effect modifiers which might influence the effect of chiropractic care for excessive crying in infancy.

Methods

Design: Prespecified secondary analyses of data from a randomised controlled trial. The analyses are partly confirmative and partly exploratory.

Setting

Four chiropractic clinics in Denmark.

Participants

Infants aged 2-14 weeks with unexplained excessive crying. Of the 200 infants randomised (1:1), 103 were assigned to a chiropractic care group and 97 to a control group.

Intervention

Infants in the intervention group received chiropractic care for 2 weeks, while the control group was not treated. Main analyses: The outcome was change in daily hours of crying. Fifteen baseline variables and 6 general variables were selected as potential effect modifiers, and indices based on these were constructed. Factor analyses, latent class analyses and prognosis were used to construct other potentially modifying variables. Finally, an attempt at defining a new index aiming at optimal prediction of the treatment effect was made. The predictive value for all resulting variables were examined by considering the difference in mean change in crying time between the two treatment groups, stratified by the values of the candidate variables, i.e. interaction analyses.

Results

None of the predefined items or indices were shown to be useful in identifying colicky infants with potentially larger gain from manual therapy. However, more baseline hours of crying (p = 0.029), short duration of symptoms (p = 0.061) and young age (p = 0.089) were all associated with an increased effect on the outcome of hours of crying.

Conclusion

Musculoskeletal indicators were not shown to be predictive of an increased benefit for colicky infants from chiropractic treatment. However, increased benefit was associated with early treatment and a high level of baseline crying, suggesting that the most severely affected infants have the greatest potential of benefiting from manual therapy. This finding requires validation by future studies.

Trial registration

Clinical Trials NCT02595515 , registered 2 November 2015.

SUBMITTER: Holm LV

PROVIDER: S-EPMC8054382 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundChiropractic care is commonly used to treat infantile colic. However large trials with parental blinding are missing. Therefore, the purpose of this study is to evaluate the effect of chiropractic care on infantile colic.MethodThis is a multicenter, single-blind randomized controlled trial conducted in four Danish chiropractic clinics, 2015-2019. Information was distributed in the maternity wards and by maternal and child health nurses. Children aged 2-14 weeks with unexplained excessive crying were recruited through home visits and randomized (1:1) to either chiropractic care or control group. Both groups attended the chiropractic clinic twice a week for 2 weeks. The intervention group received chiropractic care, while the control group was not treated. The parents were not present in the treatment room and unaware of their child's allocation. The primary outcome was change in daily hours of crying before and after treatment. Secondary outcomes were changes in hours of sleep, hours being awake and content, gastrointestinal symptoms, colic status and satisfaction. All outcomes were based on parental diaries and a final questionnaire.ResultsOf 200 recruited children, 185 completed the trial (treatment group n = 96; control group n = 89). Duration of crying in the treatment group was reduced by 1.5 h compared with 1 h in the control group (mean difference - 0.6, 95% CI - 1.1 to - 0.1; P = 0.026), but when adjusted for baseline hours of crying, age and chiropractic clinic, the difference was not significant (P = 0.066). The proportion obtaining a clinically important reduction of 1 h of crying was 63% in the treatment group and 47% in the control group (p = 0.037), and NNT was 6.5. We found no effect on any of the secondary outcomes.ConclusionExcessive crying was reduced by half an hour in favor of the group receiving chiropractic care compared with the control group, but not at a statistically significant level after adjustments. From a clinical perspective, the mean difference between the groups was small, but there were large individual differences, which emphasizes the need to investigate if subgroups of children, e.g. those with musculoskeletal problems, benefit more than others from chiropractic care.Trial registrationClinical Trials NCT02595515 , registered 2 November 2015.

Project description:BackgroundA recent randomized controlled trial (RCT) investigating the effect of chiropractic manipulation in 199 children aged 7-14 years with recurrent headaches demonstrated a significant reduction of number of days with headache and a better global perceived effect (GPE) in the chiropractic manipulation group compared to a sham manipulation group. However, potential modifiers for the effectiveness of chiropractic manipulation of children with recurrent headaches have never been identified. The present study is a secondary analysis of data from that RCT and will investigate potential effect modifiers for the benefit of chiropractic manipulation for children with headache.MethodsSixteen potential effect modifiers were identified from the literature and a summary index was prespecified based on clinical experience. Relevant variables were extracted from baseline questionnaires, and outcomes were obtained by means of short text messages. The modifying effect of the candidate variables was assessed by fitting interaction models to the data of the RCT. In addition, an attempt to define a new summary index was made.ResultsThe prespecified index showed no modifying effect. Four single variables demonstrated a treatment effect difference of more than 1 day with headache per week between the lower and the upper end of the spectrum: intensity of headache (p = 0.122), Frequency of headache (p = 0.031), sleep duration (p = 0.243), and Socioeconomic status (p = 0.082). Five variables had a treatment effect difference of more than 0.7 points on the GPE scale between the lower and the upper end of the spectrum: Frequency of headache (p = 0.056), Sport activity (p = 0.110), Sleep duration (p = 0.080), History of neck pain (p = 0.011), and Headache in the family (0.050). A new summary index could be constructed giving highest weight to History of neck pain and Headache in the family and Frequency of headache. The index suggests a difference of about 1 point in GPE between low and high values of the index.ConclusionChiropractic manipulation offers a moderate benefit for a broad spectrum of children. However, it cannot be excluded that specific headache characteristics, family factors, or a history of neck pain may modify the effect. This question must be addressed in future studies.Trial registrationClinicalTrials.gov (Albers et al in Curr Pain Headache Rep 19:3-4, 2015), identifier NCT02684916, registered 02/18/2016-retrospectively registered.

Project description:Background:Infantile colic is a common condition during early childhood affecting around one of six newborns. The condition is characterized by inconsolable crying and fussing in otherwise healthy and thriving infants. The most used definition is excessive crying for at least three hours a day for at least three days for at least three weeks. The cause of colic is still unknown although many hypotheses and thereby many different treatment modalities have been investigated. Chiropractic care is used increasingly in treatment of infants, including for infantile colic, although the evidence worldwide is sparse. A randomized, controlled trial was designed to evaluate the effect of chiropractic treatment on infantile colic. This paper describes the protocol as well as results from a pilot study examining the acceptability and feasibility of the intervention. Method:The study is designed as a single-blind randomized, controlled trial. The invited families are residents on the Island of Funen and information about the project is distributed from the maternity wards and health visitors. Children at the age of 2-14 weeks with unexplained excessive crying are screened for eligibility and recruited by the primary investigator through home visits. Eligible children are then randomized to chiropractic treatment or control. All children attend in the chiropractor clinic two times a week for two weeks. The parents are unaware of their child's allocation during the project period. The primary outcome measure is change in daily hours of crying based on the parental diaries.The study intends to include 200 children, and the intervention has, during a pilot study, been found acceptable and feasible among families with newborns. Discussion:In a single-blind randomized controlled design we will evaluate the effectiveness of chiropractic treatment on infantile colic. The study will contribute to determine the effect of chiropractic treatment on infantile colic in an area where limited evidence exists. Furthermore, the study aims to explore if subgroups of children with suspected musculoskeletal problems will benefit more from the intervention than others. If they obtain better results, this could imply the need for stratified care. Trial registration:Clinicaltrials.gov and Identifier: NCT02595515 (registered 2 November 2015).

Project description:BACKGROUND:Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previous lumbar disc herniation. METHODS:We performed analyses of effect modifiers on data from AIM, a double-blind parallel-group multicentre trial. One hundred eighty patients with chronic low back pain, previous disc herniation, Modic change type I (n?=?118) or type II (n?=?62) were randomised to 3-months oral treatment with 750?mg amoxicillin (n?=?89) or placebo (n?=?91) three times daily. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (possible values 0-24) at 1-year follow-up in the intention-to-treat population. The predefined minimal clinically important between-group mean difference was 4 RMDQ points (not reached in the primary analysis of AIM). Predefined baseline characteristics were analysed as potential effect modifiers, four primary (type I Modic changes, previous disc surgery, positive pain provocation test, high CRP) and five exploratory (disturbed sleep, constant low back pain, short duration of low back pain, younger age, and male) using ANCOVA with interaction terms. RESULTS:None of the four primary potential effect modifiers had strong evidence of modifying the treatment effect. In patients younger than 40?years the difference in mean RMDQ score between the treatment groups was -?4.0 (95%CI, -?6.9 to -?1.2), compared to -?0.5 (95%CI, -?2.3 to 1.3) in patients 40?years or older, both in favour of amoxicillin treatment (exploratory analysis). CONCLUSIONS:We did not find evidence for convincing clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes. Our results for younger age in these explorative analyses should not affect clinical treatment decisions without confirmation in future studies. TRIAL REGISTRATION:ClinicalTrials.gov NCT02323412 , First registered 23 December 2014.

Project description:BackgroundAnimal studies suggest that undercarboxylated osteocalcin may improve insulin sensitivity via its effect on testicular testosterone production. Human studies have been conflicting. Men undergoing androgen deprivation therapy (ADT) for prostate cancer experience profound hypogonadism resulting in increased insulin resistance. In a randomised controlled trial (RCT) of zoledronic acid versus placebo in men commencing extended-duration ADT, we aimed to examine the effects on fat mass and glucose metabolism. We hypothesised that zoledronic acid, which reduces osteocalcin concentrations, would worsen ADT-induced insulin resistance.MethodsThis was a prespecified secondary analysis of an RCT designed to evaluate the effects of zoledronic acid on bone microarchitecture in 76 men with non-metastatic prostate cancer undergoing curative radiotherapy combined with adjuvant ADT (n = 39 randomised to a single dose of zoledronic acid 5 mg, n = 37 randomised to matching placebo). Oral glucose tolerance tests to determine Matsuda Index were performed at 0, 3, 12 and 24 months. Using a mixed model, mean adjusted differences [MAD (95% confidence interval)] between the groups over time are reported.ResultsOver 24 months of ADT, fat mass increased and lean mass decreased for both groups, with no significant between group difference [MAD 401 g (-1307; 2103), p = 0.23 and -184 g (-1325; 955), p = 0.36 respectively]. Bone remodelling markers C-telopeptide [MAD -176 ng/l (-275; -76), p < 0.001 and P1NP -18 mg/l (-32; -5), p < 0.001] as a surrogate for osteocalcin, remained significantly lower in the zoledronic acid group, compared with placebo. There was no mean adjusted between-group difference for homeostatic model assessment 2 insulin resistance (HOMA2-IR) [-0.2 (-0.6; 0.2), p = 0.45], HbA1c [-0.1% (-0.3; 0.1), p = 0.64] or Matsuda Index [0.8 (-1.1; 2.7), p = 0.38]. The Matsuda Index decreased in both groups consistent with worsening insulin resistance with ADT.ConclusionA single dose of zoledronic acid does not appear to influence glucose metabolism in men newly commencing ADT. Further study to evaluate the endocrine relationship between bisphosphonates, bone and glucose metabolism is required.Trial registration number[ClinicalTrials.gov identifier: NCT01006395].

Project description:BackgroundTo investigate the effectiveness of chiropractic spinal manipulation versus sham manipulation in children aged 7-14 with recurrent headaches.MethodsDesign: A two-arm, single-blind, superiority randomised controlled trial.SettingOne chiropractic clinic and one paediatric specialty practice in Denmark, November 2015 to August 2020.Participants199 children aged 7 to 14?years, with at least one episode of headache per week for the previous 6?months and at least one musculoskeletal dysfunction identified.InterventionsAll participants received standard oral and written advice to reduce headaches. In addition, children in the active treatment group received chiropractic spinal manipulation and children in the control group received sham manipulation for a period of 4?months. Number and frequency of treatments were based on the chiropractor's individual evaluation in the active treatment group; the children in the control group received approximately eight visits during the treatment period.Primary outcome measures'Number of days with headache', 'pain intensity' and 'medication' were reported weekly by text messages, and global perceived effect by text message after 4?months. A planned fixed sequence strategy based on an initial outcome data analysis was used to prioritize outcomes. 'Number of days with headache' and 'pain intensity' were chosen as equally important outcomes of highest priority, followed by global perceived effect and medication. The significance level for the first two outcomes was fixed to 0.025 to take multiplicity into account.ResultsChiropractic spinal manipulation resulted in significantly fewer days with headaches (reduction of 0.81 vs. 0.41, p?=?0.019, NNT?=?7 for 20% improvement) and better global perceived effect (dichotomized into improved/not improved, OR?=?2.8 (95% CI: 1.5-5.3), NNT?=?5) compared with a sham manipulation procedure. There was no difference between groups for pain intensity during headache episodes. Due to methodological shortcomings, no conclusions could be drawn about medication use.ConclusionsChiropractic spinal manipulation resulted in fewer headaches and higher global perceived effect, with only minor side effects. It did not lower the intensity of the headaches. Since the treatment is easily applicable, of low cost and minor side effects, chiropractic spinal manipulation might be considered as a valuable treatment option for children with recurrent headaches.Trial registrationClinicalTrials.gov, identifier NCT02684916 , registered 02/18/2016 - retrospectively registered.

Project description:Background:In children, spinal pain is transitory for most, but up to 20% experience recurrent and bothersome complaints. It is generally acknowledged that interventions may be more effective for subgroups of those affected with low back pain. In this secondary analysis of data from a randomized clinical trial, we tested whether five indicators of a potential increased need for treatment might act as effect modifiers for manipulative therapy in the treatment of spinal pain in children. We hypothesized that the most severely affected children would benefit more from manipulative therapy. Method:This study was a secondary analysis of data from a randomised controlled trial comparing advice, exercises and soft tissue treatment with and without the addition of manipulative therapy in 238 Danish school children aged 9-15?years complaining of spinal pain. A text message system (SMS) and clinical examinations were used for data collection (February 2012 to April 2014).Five pre-specified potential effect modifiers were explored: Number of weeks with spinal pain 6?months prior to inclusion, number of weeks with co-occurring musculoskeletal pain 6?months prior to inclusion, expectations of the clinical course, pain intensity, and quality of life.Outcomes were number of recurrences of spinal pain, number of weeks with pain, length of episodes, global perceived effect, and change in pain intensity. To explore potential effect modification, various types of regression models were used depending on the type of outcome, including interaction tests. Results:We found that children with long duration of spinal pain or co-occurring musculoskeletal pain prior to inclusion as well as low quality of life at baseline tended to benefit from manipulative therapy over non-manipulative therapy, whereas the opposite was seen for children reporting high intensity of pain. However, most results were statistically insignificant. Conclusions:This secondary analysis indicates that children more effected by certain baseline characteristics, but not pain intensity, have a greater chance to benefit from treatment that include manipulative therapy. However, these analyses were both secondary and underpowered, and therefore merely exploratory. The results underline the need for a careful choice of inclusion criteria in future investigations of manipulative therapy in children. Trial registration:NCT01504698; results.