title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Defocus curves and area-of-focus metric | Defocus curves under monocular uncorrected visual acuity showed that group A achieved higher VAs over +1.00 D to -3.00 D than group B (- The defocus curves and the area-of-focus metric of the 2 groups. | PMC10187746 | ||
Subjective visual quality | visual disturbance, photophobia, abnormal color vision | LENS | The VF-14-questionnaire aggregate score of group A was statistically higher than that of group B (Most patients did not have an obvious visual disturbance after surgery. Two patients in group A developed abnormal color vision and mild photophobia after surgery, and the symptoms were relieved 3 months post-surgery, while another patient with foreign body sensation did not show a noticeable improvement. In group B, 3 patients experienced ocular foreign body sensation and mild photophobia after surgery, which was significantly improved 3 months after the surgery; no statistically significant difference was observed between the 2 groups.- The MTF average height, SR, and DLI at 3 months after surgery with LISA tri 839MP and Mi60.n represented the number of eyes followed up after surgery,MTF: modulation transfer function,SR: Strehl ratio,DLI: dysfunctional lens index | PMC10187746 |
Objective visual quality | The comparison of MTF average height values at the same spatial frequencies | PMC10187746 | ||
Discussion | Cataract, cataracts, visual impairment, cataract, abnormal color vision, IOL, corneal irregular astigmatism | CATARACT, IOL, GROUP B, NEAR VISION, RECRUITMENT, CATARACT, LENS, CATARACTS | Cataract extraction combined with IOL implantation is the only effective method for the treatment of cataracts at present. Patients put forward higher requirements for the postoperative effect of cataracts to meet the needs and improve the quality of life. A previous studyTypically, doctors implanted monofocal IOL for patients during cataract surgery, which could provide good distance only. Thus, the patients required spectacles correction for intermediate and near vision postoperatively. The emergence of trifocal IOL makes it possible for patients to have spectacles independence after surgery. Trifocal IOL can converge parallel light into far, intermediate, and near focus and provide a good functional vision at all distances with high levels of spectacles independence and patient satisfaction. In the current study, group A (with 839MP) had better monocular UCVA in the distance, intermediate, and near vision, while BCVA had no difference.When different types of IOLs were implanted, statistically significant differences were detected in the area-of-focus metric between groups A and B in the distance area, intermediate area, and near area. The range from 0-4.34 mm diameter center is +1.66 D, +3.33 D, with additional medium and near vision trifocal design, and that for 4.34-6 mm is +3.33 D bifocal designed with additional near vision. This design results in wider and better vision after trifocal IOL implantation, which in turn, leads to better visual function, higher satisfaction, spectacles independence, and quality of life, especially in the intermediate and near distance. The study by Tarib et alAlthough the contrast sensitivity values of patients with scotopic and photopic vision after trifocal IOL implantation were within the normal range, Group B had significantly higher CSF under UCVA at 3 months after the operation in our study.Due to the diffraction design of this trifocal IOL, patients had more visual interference after implantation, especially glare and halos. However, no statistical difference was detected in the visual interference between the 2 groups. This may be related to the special design of the trifocal IOL, making it to have high light energy utilization. Interestingly, we found that 2 patients in group A had an abnormal color vision after implantation, and their vision was slightly bluish, while no patient reaction was noted in group B. This phenomenon could be attributed to the diffraction ring design of this trifocal IOL. The height of the diffraction step of IOL with different diopters determined the passage of specific diffracted light waves, while the wavelengths of light of different colors varied, resulting in abnormal color vision in some patients due to the diffraction of light waves after implantation. However, this part of the abnormality could be gradually alleviated after brain fusion and adaptation and did not affect the patient’s daily life. Nonetheless, this finding needs to be substantiated further. However, this study was limited by the sample size and the recruitment of patients from only one hospital.In conclusion, compared to monofocal intraocular lens, the trifocal intraocular lens provides a full range of clear vision for the majority of patients with simple cataracts and improves the rate of spectacle independence and patients’ satisfaction, but reduces the patients’ contrast sensitivity and cause visual impairment. However, the objective quality of vision did not show any difference and would not significantly affect the daily life of the patients. Despite visual interference, trifocal intraocular lenses are preferred by patients. By strictly controlling the indications of trifocal intraocular lenses implantation, such as spherical aberration, the total corneal irregular astigmatism in 4-mm area, and the kappa angle, this visual interference can be reduced to a minimum and would not affect the daily life of patients. | PMC10187746 |
Acknowledgment | PMC10187746 | |||
References | PMC10187746 | |||
Objective: | To study the effect of the birthing room design on nulliparous women’s childbirth experience up to 1 year after birth. | PMC9755691 | ||
Background: | Although it is known that the birth environment can support or hinder birth processes, the impact of the birthing room design on maternal childbirth experience over time is insufficiently studied. | PMC9755691 | ||
Methods: | The Room4Birth randomized controlled trial was conducted at a labor ward in Sweden. Nulliparous women in active stage of spontaneous labor were randomized ( | PMC9755691 | ||
Results: | Women randomized to the new room had a more positive childbirth experience reported on the VAS-OCE 3 months ( | PMC9755691 | ||
Method | PMC9755691 | |||
Study Design and Setting | This study reports women’s childbirth experiences 2 hr, 3 months, and 12 months after participation in the Room4Birth randomized controlled superiority trial (RCT) in Sweden (Randomization was undertaken between January 2019 and October 2020 at a labor ward located in western Sweden and with an annual birth rate of around 4,000 births (Photos of (A) one of the regular birthing rooms and (B) the new birthing room.New birthing room where the medico-technical devices were hidden behind wood-paneled walls (A) that could be rolled up if required (B). | PMC9755691 | ||
Sample and Recruitment | RECRUITMENT | Eligible participants for randomization were women aged 18 or more, classified as Robson 1 (Participant recruitment was carried out by the midwives and assistant nurses at the labor ward. Eligible women were asked to participate after labor ward arrival and confirmed active stage of labor, if both a regular room and the new room were vacant. All women gave signed, written consent to participate, and the time interval from labor ward arrival to randomization was set to be as short as possible to ensure an early allocation to the randomized room. The randomly computer-generated allocation list was managed by an independent agency. Information about the allocated room was printed in sealed, opaque envelopes sequentially placed in a study box at the labor ward. The recruiting care provider was not aware of the randomization sequence, and the independent agency ensured that the allocation list was followed. The women were provided with a four-digit ID code, which was printed on the sealed envelope. | PMC9755691 | |
Data Collection and Outcome Measures | Participants’ demographic data were collected from obstetric records and through a self-reported, digital questionnaire 2 hr after birth (After 3 (Overview of data collection. Participants’ self-reported experiences on a Visual Analogue Scale of Overall Childbirth Experience (VAS-OCE), Fear of Birth Scale (FOBS), and Childbirth Experience Questionnaire version 2 (CEQ2).Assessing overall childbirth experience by using a VAS (continuous data) ranging from 1 to 10, where 10 is most positive, is routinely used in Sweden (To assess fear during birth and of a potential future birth, a modified FOBS was used. In its original form (The CEQ2 ( | PMC9755691 | ||
Statistical Analysis | REGRESSION | To compare differences between the two randomized groups, χA linear mixed effects model was used to describe the group differences in childbirth experience over the three time points. This regression model was chosen since it can provide information about the women’s individual change in childbirth experience over time but is also flexible since it has the capability to handle missing observations in the repeated measures data ( | PMC9755691 | |
Results | The study sample consisted of 406 women, where 204 were randomized to the new room and 202 to the regular room (CONSORT flow chart of randomization and follow-up. The demographic characteristics of the responders to the follow-up questionnaires did not differ between the randomized groups (Participants’ Demographic Information.
* Statistically significant difference between groups. | PMC9755691 | ||
Self-Reported Childbirth Experience | The women’s overall childbirth experience on a VAS-OCE 2 hr after birth was similar in both randomized groups, as previously presented (Overall Childbirth Experience (VAS-OCE) and Fear of Birth (FOBS) 2 hr, 3 Months, and 12 Months After Birth.
Women in the new room scored higher within the CEQ2 domain Participants’ Childbirth Experience Questionnaire (CEQ2) Scores 3 And 12 Months After Birth.
| PMC9755691 | ||
Childbirth Experience Measured Over Time | The childbirth experience scored on a VAS-OCE decreased at 3 months (Childbirth experience 2 hr, 3 months, and 12 months after birth in the two randomized groups measured with a linear mixed-effects model. (A) Visual Analogue Scale of Overall Childbirth Experience (VAS-OCE) 1–10, (B) fear during past childbirth on a Fear of Birth Scale (FOBS) 0–100, and (C) fear of giving birth again on a FOBS 0–100.Childbirth Experience Questionnaire (CEQ2) values (1–4) within the four domains (The significant effect of the new room in the CEQ2 subdomain | PMC9755691 | ||
Methodological Considerations | The advantages of our study include its randomized design and the high response rates of the follow-up questionnaires. Another strength is that the participants were asked to report their childbirth experiences at three different time points during their first year after birth. This made it possible to study how the experience of birth changes over time. Unfortunately, this study had a limited sample size, which was not sufficient to detect an effect in the 12-month follow-up. The sample size estimation was based on the primary outcome of the Room4Birth RCT (To explore the multidimensional phenomenon of childbirth experience, we chose to include three different measurements (VAS-OCE, FOBS, and CEQ2). Nevertheless, it is challenging to measure experiences quantitatively, since aspects such as context, social support, interpersonal relationships, and physical and emotional senses need to be taken into consideration (The place and space for birth is not just created through the physical design but also through those who inhabit and interact within the room ( | PMC9755691 | ||
Conclusion | The findings of this study show the benefit of acknowledging the physical design of hospital-based birthing rooms. Nulliparous women randomized to a birthing room designed with person-centered considerations aimed at supporting the physiology of birth reported more positive overall childbirth experiences 3 and 12 months after birth than women randomized to a regular birthing room. When designing interventions and environments in hospital settings, it is essential to understand the psychological and existential dimensions of childbirth, since the dynamics and changes in labor and birth experiences influence outcomes. It is also essential to understand how remnants of archaic nest-building behaviors and experiences are still present in birthing women of today. The findings of the study confirm that the physical design matters to women in their assessment of childbirth experience, but we were unable to show the actual effect of the new room on the variables explored. Therefore, additional research is needed that qualitatively explores the impact of the birth environment design on women’s long-term childbirth experiences. | PMC9755691 | ||
Implications for Practice | From a mental health perspective, it is essential to understand the importance of emotional well-being in the transition to parenthood.A birthing room designed with person-centered considerations, where women and companions can adapt features and functions in the room in accordance with personal needs and requirements, positively impacts women’s birth experiences 3 and 12 months after birth.When striving to optimize care during labor and birth, both the physical and the psychosocial environment need to be improved.To value emotions, birth physiology and person-centered perspectives in labor ward design may be one strategy to help reverse the rising trend of medical interventions in labor that is observed in many hospital settings. | PMC9755691 | ||
Supplemental Material | PMC9755691 | |||
Supplemental Material, sj-pdf-1-her-10.1177_19375867221124232 - Impact of Birthing Room Design on Maternal Childbirth Experience: Results From the Room4Birth Randomized Trial | Click here for additional data file.Supplemental Material, sj-pdf-1-her-10.1177_19375867221124232 for Impact of Birthing Room Design on Maternal Childbirth Experience: Results From the Room4Birth Randomized Trial by Lisa Goldkuhl, Hanna Gyllensten, Cecily Begley, Christina Nilsson, Helle Wijk, Göran Lindahl, Kerstin Uvnäs-Moberg and Marie Berg in HERD: Health Environments Research & Design Journal | PMC9755691 | ||
References | PMC9755691 | |||
Background | chemotherapy-associated insomnia, breast cancer, Acupuncture, insomnia, Insomnia | BREAST CANCER | Insomnia is a highly prevalent symptom occurred during and post-chemotherapy. Acupuncture may have beneficial effects in the management of chemotherapy-associated insomnia. This study was conducted to determine the efficacy and safety of acupuncture in improving chemotherapy-associated insomnia in breast cancer patients. | PMC10134666 |
Methods | chemotherapy-associated insomnia, anxiety, breast cancer, fatigue, pain, Insomnia, depression | BREAST CANCER | This assessor-participant blinded, randomized, sham-controlled trial was conducted from November 2019 to January 2022 (follow-up completed July 2022). Participants were referred by oncologists from two Hong Kong hospitals. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, the University of Hong Kong. The 138 breast cancer patients with chemotherapy-associated insomnia were randomly assigned to receive either 15 sessions of active acupuncture regimen by combining needling into body acupoints and acupressure on auricular acupoints or sham acupuncture control (69 each) for 18 weeks, followed by 24 weeks of follow-up. The primary outcome was measured using Insomnia Severity Index (ISI). Secondary outcomes included the Pittsburgh Sleep Quality Index, Actiwatch and sleep diary for sleep parameters, depression and anxiety, fatigue and pain, and quality of life. | PMC10134666 |
Results | There were 87.7% (121/138) participants who completed the primary endpoint (week-6). The active acupuncture regimen was not superior to the sham control in reducing ISI score from baseline to 6 weeks (mean difference: − 0.4, 95% CI − 1.8–1.1; | PMC10134666 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s13058-023-01645-0. | PMC10134666 | ||
Keywords | PMC10134666 | |||
Background | Breast cancer, insomnia, cancer and cancer-related symptoms | MALIGNANCIES, BREAST CANCER | Breast cancer patients are at significantly greater risk of developing insomnia than those with other malignancies and the general population [Over the past two decades, acupuncture has gained increasing popularity in the treatment of insomnia, cancer and cancer-related symptoms [ | PMC10134666 |
Methods | PMC10134666 | |||
Design and settings | WEST, RECRUITMENT, RECRUITMENT | This was an assessor-participant-data analyst blinded, randomized, sham-controlled trial. The trial was approved by Institutional Review Board of the University of Hong Kong (HKU)/Hospital Authority Hong Kong (HK) West Cluster (UW 19-045) and Research Ethics Committee of HK Sanatorium & Hospital (REC-2019-14). The trial was registered in Recruitment and treatment occurred between November 2019 and January 2022; follow-up assessments completed in July 2022. Participants were referred by oncologists from HK Queen Mary Hospital and HK Sanatorium & Hospital. Multiple promotions were carried out to facilitate recruitment, including advertising on newspapers and Facebook. Participants gave voluntary, written, informed consent after study procedures were fully explained. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, HKU. | PMC10134666 | |
Participants | sleep disorders, hearing, visual or language defects, hematological dysfunction, insomnia, Insomnia, electroacupuncture, insomnia disorder | DISORDERS, OBSTRUCTIVE SLEEP APNOEA, BREAST CANCER | Patients were eligible if they were: (i) females aged 18–75; (ii) had a diagnosis of stage I–IV breast cancer; (iii) underwent or had completed chemotherapy no more than 6 months; (iv) insomnia occurred at least 3 nights/week and lasted at least one month, with the fulfilment of the diagnostic criteria for brief insomnia disorder of the Diagnostic and Statistical Manual of Mental Disorders (5th Edition); and (v) the severity of insomnia reached at least 10 points of Insomnia Severity Index (ISI) over the past 2 weeks.Patients were excluded if they had: (i) other sleep disorders (e.g., obstructive sleep apnoea), irregular sleep pattern, or shift work; (ii) severe hearing, visual or language defects; (iii) severe hematological dysfunction (e.g., haemoglobin < 8 g/dL, platelet count < 60,000/μL, absolute neutrophil count < 1000/μL); (iv) pacemakers or other electronic implants that might interfere with electroacupuncture; (v) had acupuncture treatment in the past 3 months; or (vi) participated in other clinical trials in the past 3 months. | PMC10134666 |
Randomization | Permuted block randomization (block sizes of 2/4/6) was used. After baseline assessments, participants were randomly assigned to two groups at a ratio of 1:1 according to the randomization sequence. The randomization sequence was generated by an independent biostatistician using Microsoft Excel prior to study initiation. Individual randomization code was sealed in sequentially numbered opaque envelopes and opened by acupuncturist after participants completed baseline assessments. | PMC10134666 | ||
Blinding and allocation concealment | INTERACTIONS, EYE | Investigators and research staffs who performed screening, assessments, and data entry/re-entry/analysis were blinded to group allocation. Participants were informed that they would have same chance of allocating to either group and would be blinded to allocation. Treatment was delivered individually in a separate room to avoid communications among participants about treatment experience. Eye mask was used to block participant’s vision during treatment so that she was unaware of acupuncture procedure. Acupuncturists were instructed not to acquire participants’ information except group allocation. Interactions between acupuncturists and participants were kept to a minimum to avoid accidental disclosure of group allocation. | PMC10134666 | |
Intervention | Acupuncture | Participants continued routine care and symptom management during study. Acupuncture treatment was carried out by registered Chinese Medicine Practitioners (CMPs) had at least 5-year clinical practice experience and completed training workshop prior to study initiation. The training workshop included introduction of treatment protocol, standard procedures of active and sham acupuncture, and conversation skills with participants. The treatment protocol [ | PMC10134666 | |
Active acupuncture regimen | comorbid symptoms, insomnia | Active acupuncture regimen consisted of electroacupuncture on body acupoints and auricular acupressure. Six fixed acupoints (EX-HN1, GV20, GV24, PC6, KI3 and SP6) were utilized for treating insomnia [Recommendation of additional acupoints based on comorbid symptoms | PMC10134666 | |
Sham acupuncture regimen | Sham points that are located at 1–2 cm adjacent to meridian-based acupoints were used for sham electroacupuncture [ | PMC10134666 | ||
Concomitant use of psychotropic medications | Psychotropic medications were allowed to be prescribed at the discretion of psychiatrists and general physicians during study. The proportion of participants who were prescribed with sleeping medications (sedatives, hypnotics and anxiolytics), dosage and weekly frequency of use were recorded. The dosage used was converted as diazepam equivalent dosage. Four mean dosages were obtained by averaging across a 2 week duration [ | PMC10134666 | ||
Assessments | PMC10134666 | |||
Primary outcome | Details of outcomes have been reported previously [ | PMC10134666 | ||
Secondary outcomes | Anxiety, fatigue, anxiety, pain, depressive, depression/anxiety, depression, Depression | Secondary outcomes included sleeping measures, depression and anxiety, fatigue and pain, and quality of life. Actiwatch [The severity of depression/anxiety was measured using Hospital Anxiety and Depression Scale (HADS) which is a 14-item questionnaire with two subscales to evaluate the severity of depressive and anxiety symptoms [ | PMC10134666 | |
Adverse events | ADVERSE EVENT | Adverse events (AEs) were recorded during study. Whether an AE related to treatment was determined by acupuncturists. Serious AEs were immediately reported to principal investigator and Ethics Committee within 24 h of the occurrence. | PMC10134666 | |
Credibility, expectancy, adherence, and successiveness of blinding | The credibility of treatment was assessed using the 4-item, 6-point Credibility Rating Scale [ | PMC10134666 | ||
Data security and monitoring | All data were secured in compliance with HK Personal Data (Privacy) Ordinance (CAP 486). A data and safety monitoring board (DSMB) was established [ | PMC10134666 | ||
Statistical analysis | PMC10134666 | |||
Estimation of sample size | non-cancer, primary insomnia, chemotherapy-associated insomnia, breast cancer | PRIMARY INSOMNIA, BREAST CANCER | There was no study has previously been conducted in the female with breast cancer experiencing chemotherapy-associated insomnia. The sample size was estimated based on anticipated changes of ISI score. Based on previous trials among non-cancer population with primary insomnia [ | PMC10134666 |
Data analysis | The efficacy was analyzed in the intention-to-treat population, defined as participants who completed baseline assessments. For missing data, the multiple imputation method was used under the missing-at-random (MAR) assumption. The sensitivity of MAR assumption of missing data was tested with a pattern-mixture model [Categorical variables, including categorical baseline variables, cessation rate of sleeping medications and incidence of AEs, were analyzed using Chi-square or Fisher’s exact tests. Unpaired | PMC10134666 | ||
Results | PMC10134666 | |||
Cessation rate and sleeping medications used | The active acupuncture group had a higher cessation rate of sleeping medication during 18–20 weeks than the sham control (56.5% vs. 14.3%, Cessation rate over time. * | PMC10134666 | ||
Secondary outcomes | Secondary outcomes are summarized in Table | PMC10134666 | ||
Adverse events | Treatment-related AEs were mild (Additional file | PMC10134666 | ||
Credibility for treatment and blinding design | Credibility score for treatment was not significantly different between groups (Additional file | PMC10134666 | ||
Discussion | chemotherapy-associated insomnia, anxiety, breast cancer, chemotherapy-induced cognitive decline, insomnia, electroacupuncture, depression | BREAST CANCER | The main purpose of this trial was to determine whether the active acupuncture regimen could produce superior efficacy over the sham control in improving chemotherapy-associated insomnia in breast cancer patients. Following 12 sessions of treatment, participants on the active acupuncture regimen showed significantly greater improvements than sham control in sleep onset latency, total sleep time and sleep efficiency, which were examined daily with the objective assessment Actiwatch and subjective assessment diary. Likewise, it is evidenced that active acupuncture was markedly associated with improvements in objective sleep parameters, including increases in total sleep time and sleep efficiency [Participants on the active acupuncture regimen achieved better treatment outcomes than those on the sham control in reducing comorbid anxiety and depression and improving quality of life during treatment and follow-up. Similar results have been observed in recent trial that demonstrated the superior efficacy of active acupuncture regimen in improving chemotherapy-induced cognitive decline, distress caused psychological and somatic symptoms and social functions in breast cancer patients [Moreover, in a follow-up period of 18–20 weeks, a much greater proportion of the participants in the active acupuncture group stopped taking sleeping medications than the sham control group. Our previous study, nonetheless, displayed no difference in cessation rate in long-term benzodiazepine users between electroacupuncture and non-invasive placebo control [Similar to previous studies [Several possible mechanisms have been proposed to understand the effect of acupuncture for cancer-related insomnia. First, acupuncture can regulate cerebral neurotransmitters associated with sleep regulation, such as gamma aminobutyric acid, 5-hydroxytryptamine, dopamine, noradrenaline, acetylcholine, histamine and orexin [The efficacy of treatments might be affected by the precipitating or perpetuating factors of chemotherapy-associated insomnia [The sham control produced greater improvement in ISI score after 6-week of intervention than other sham-controlled acupuncture trials [One should consider the following limitations of this study. Firstly, although Streitberger’s retractable placebo needles have been widely used to differentiate specific effects of inserted acupuncture from non-inserted needles, it still could produce widespread modulatory effects at multiple levels of central nervous system by exciting mechanoreceptors underneath skin via pressure from non-inserted needles [ | PMC10134666 |
Conclusion | chemotherapy-associated insomnia, anxiety, breast cancer, insomnia, depression | BREAST CANCER | The active acupuncture regimen produced better outcomes than the sham control in improving sleep onset latency, total sleep time and sleep efficiency in breast cancer women with chemotherapy-associated insomnia, although there was no significant difference in reducing insomnia severity. Active acupuncture had significantly greater effects in improving anxiety, depression and quality of life. Participants of the active acupuncture group showed a markedly higher cessation rate of sleeping medications. Active acupuncture regimen could be considered as an effective option for chemotherapy-associated insomnia and a tapering approach to reduce and even replace use of sleeping medications in breast cancer patients. | PMC10134666 |
Acknowledgements | ONCOLOGY | We acknowledge the DSMB members, Dr. Chi Ho Chung (The Jockey Club School of Public Health and Primary Care Faculty of Medicine, the Chinese University of Hong Kong), Dr. Tai Chung Lam (Department of Clinical Oncology, HKU), and Dr. Jihui Zhang (Department of Psychiatry, The Chinese University of Hong Kong) for reviewing study design and monitoring trial progress. We thank all participants for their valuable support to this trial. We thank Ms. Lo Lo Yam, Miss Wai Nga Chung and Miss Yuting Ying for their assistance in performing treatments, and all research staffs for their dedication to the research process. | PMC10134666 | |
Author contributions | WFY | JLZ drafted the manuscript. ZJZ, LXL, JLZ, HYC, THS, TYC, KFC, and WFY participated in study design. THS and TYC referred participants. ZSQ conducted data analysis. ZJZ revised the manuscript. JLZ and SCY carried out treatments. PYC performed assessments. SFX, YH, CYC provided critical comments. All authors approved the final manuscript. | PMC10134666 | |
Funding | This trial was funded by Health and Medical Research Fund, Government of the Hong Kong Special Administrative Region of China (Ref no: 16172761). The funding body was not involved in study design and conduct, data collection, management, analysis and interpretation. | PMC10134666 | ||
Availability of data and materials | The data underlying this article will be shared on reasonable request addressed to zhangzj@hku.hk. | PMC10134666 | ||
Declarations | PMC10134666 | |||
Ethics approval and consent to participate | WEST | The trial was approved by Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 19-045) and Research Ethics Committee of Hong Kong Sanatorium & Hospital (REC-2019-14). The research was carried out in accordance with the Declaration of Helsinki. | PMC10134666 | |
Consent for publication | Not applicable. | PMC10134666 | ||
Competing interests | The authors declared no potential competing interests with respect to the research, authorship, and publication of this article. | PMC10134666 | ||
References | PMC10134666 | |||
Methods: | This was a | PMC10254966 | ||
Results: | Subjects ( | PMC10254966 | ||
Conclusion: | The overall effects of SDX/d-MPH on growth velocity (the change in weight and height from one time point to the next) were minimal, and the range of changes was not considered clinically significant. | PMC10254966 | ||
Introduction | attention-deficit/hyperactivity disorder, ADHD | SPENCER, GROWTH SUPPRESSION | Methylphenidate (MPH) is a commonly prescribed medication for attention-deficit/hyperactivity disorder (ADHD) because of its efficacy for symptom reduction and overall favorable safety record. MPH is often prescribed for long-term use in patients with ADHD (Storebø et al. This formulation of SDX/d-MPH (Azstarys™; Corium, LLC, Boston, MA) was approved by the US Food and Drug Administration for patients aged 6 years and older with ADHD.In a pivotal, randomized, placebo-controlled, double-blind laboratory classroom study of children with ADHD, SDX/d-MPH treatment was shown to significantly improve ADHD symptoms compared with placebo (Kollins et al. A subsequent, 1-year, open-label safety study of SDX/d-MPH in children with ADHD showed that SDX/d-MPH was well tolerated and had sustained efficacy during the 1-year treatment period (Childress et al. Long-term treatment with stimulants, such as MPH for ADHD, in children has been associated with modest slowing of growth velocity and prescribing information for these treatments warns of long-term growth suppression, which can cause concern and limit their use (Spencer et al. | PMC10254966 |
Methods | This | PMC10254966 | ||
Subjects | ADHD | The subjects were children aged 6–12 years with ADHD at the start of the dose-optimization (DO) phase of the study. Subjects included those rolled over from the antecedent pivotal study (Kollins et al. | PMC10254966 | |
Study design | The study design included a 30-day screening phase, a 3-week DO phase, a 360-day treatment phase, and a follow-up visit. Only new subjects underwent screening and DO. During the DO phase, new subjects were titrated to their optimized dose based on the best dose response and individual tolerability to the treatment (Childress et al. New subjects started treatment with the 39.2/7.8 mg dose of SDX/d-MPH daily, which is a molar equivalent to 30 mg of total d-MPH HCl, for 7 days. If needed, dose adjustments were performed based on the investigator's assessment of the subject at weekly intervals. The SDX/d-MPH dose could be increased to 52.3/10.4 mg (40 mg molar equivalent of total d-MPH HCl), decreased to 26.1/5.2 mg (20 mg molar equivalent of total d-MPH HCl), or maintained at the same dose for the next week of dosing.The dose at the end of the third week was assigned as the optimized dose. Subjects who rolled over from the pivotal study remained on their optimized dose from that study. The optimized SDX/d-MPH dose was used during the treatment phase. All subjects were administered 1 capsule daily of their optimized dose of SDX/d-MPH. Weight and height analyses were conducted in the treatment phase safety population of enrolled subjects. This population included those who received at least 1 dose of study medication and had at least 1 postdose safety assessment in the treatment phase. Completers are those subjects that completed 12 months of treatment. | PMC10254966 | ||
Weight and height measurements | Body weight (in kg) and height (in cm) were measured at each monthly visit. Body weight was measured using a calibrated scale while subjects remained in their normal clothing, with shoes and jacket (and/or outer clothing) removed. Height was measured using a stadiometer with the subject's shoes removed. | PMC10254966 | ||
Results | PMC10254966 | |||
Subject disposition | Subject disposition has been previously described (Childress et al. Subject disposition. | PMC10254966 | ||
Subject demographics and baseline characteristics | SD | The mean (SD) age for the subjects was 9.1 (1.9) years; 60.9% of the subjects were male, and 39.1% were female. The mean (SD; minimum, maximum) for weight was 38.6 (13.9; 21.0, 97.0) kg, BMI was 19.2 (4.6; 13.1, 37.5) kg/mSubjects' Demographics. Treatment Phase Safety PopulationSD, standard deviation. | PMC10254966 | |
Growth velocity | PMC10254966 | |||
Weight | weight loss | The mean (SD) body weight at baseline was 38.6 (13.9) kg with a Mean observed body weight versus mean predicted body weight Baseline Observed Mean Body Weight and Height, Predicted Weight and Height, Weight and Height Z-Score, and Weight and Height Percentiles: Treatment Phase Safety PopulationSD, standard deviation.At 90 days, the mean observed weight and predicted weight were 38.5 and 40.2 kg, respectively, with a difference between the means of 1.7 kg. At the end of the study (360 days), the mean observed weight and predicted weight were 41.1 and 42.8 kg, respectively, with the same difference between the means of 1.7 kg as after 3 months of treatment.The mean (SD) weight For subjects who completed the study, smaller decreases or lower-than-expected increases were observed during the second and third months, after which the weight velocity resumed, although at a lower starting weight at 90 days. The average weight decreased from the 68.4 (27.4) percentile to the 64.3 (28.8) percentile during the first month in the treatment phase, with an additional small decrease to the 62.8 (27.7) percentile by 12 months (Approximately the same mean weight percentile was maintained for the remainder of the study. The percentage of subjects with clinically notable weight loss, defined as a weight decrease from baseline >7%, was 8.7% at 30 days. The percentage of subjects with weight loss increased over time, peaking at 14.5% of subjects at 4 months and then declining to 5.2% of subjects at the end of the study (360 days). This time course is consistent with average weight loss observed during the beginning of the treatment phase followed by weight gains later in the study.The mean weight Mean weight The Z-scores for subjects with a baseline BMI <16.1 kg/m | PMC10254966 | |
Height | height gain | The mean (SD) height at baseline was 139.6 (11.9) cm with a A comparison of observed height versus predicted height showed a steady increase of the mean observed height over time, which was at a lower rate than the predicted velocity of height gain at each monthly visit (Mean observed height versus mean predicted height Mean height Mirroring the mean height Z-score, the mean height percentile steadily decreased, with the mean (SD) height percentile decreasing from the 64.9 (26.6) to the 60.7 (27.7) percentile after 6 months in the treatment phase and to the 57.0 (27.7) percentile at 12 months (The mean baseline height Z-scores were 0.18, 0.53, 0.51, and 0.96, for baseline BMI quartiles 1, 2, 3, and 4, respectively (Mean height | PMC10254966 | |
Discussion | weight gain, Spencer, ADHD | SPENCER, DRUG EFFECT | The safety and tolerability results from this 1-year open-label study of SDX/d-MPH in children with ADHD have been previously reported (Childress et al. Other studies of MPH in children with ADHD also observed similarly higher baseline weight and height than their reference samples (Swanson et al. A The mean weight changes as a percent from baseline-by-baseline BMI quartile groups showed that all four baseline BMI quartile groups had an initial weight decrease during the first to fourth months in the treatment phase, with a notable smaller and shorter weight decrease in baseline BMI quartile 1 compared with the other three baseline BMI quartile groups.The relative weight gain after the initial decline through the end of treatment was higher in subjects in the first and second baseline BMI quartile groups compared with subjects in the third and fourth baseline BMI quartile groups. This difference in weight gain indicates that subjects with a higher baseline BMI experienced a larger initial reduction in weight gain than subjects with a lower baseline BMI. Relative weight gain after ∼3 months of treatment appeared similar between all baseline BMI quartiles.With respect to height, the positive mean baseline height The change in height The effects of long-term treatment of stimulants on weight and height in pediatric patients are well documented (Spencer et al. However, that study was of a much shorter span than the current study, consisting of a 3-week dose optimization phase followed by a 2-week maintenance phase, and it is possible that study had not reached maximum effect on body weight that may have been measured later in treatment had the treatment continued.In a 21-month study with a dose-optimized long-acting MPH formulation in 407 children aged 6–13 years with ADHD (Spencer et al. In a more recent 12-month open-label safety study of extended-release MPH in children aged 4–5 years with ADHD, subjects entering the study were heavier and taller than the reference population (Childress et al. In the extended-release MPH study (Childress et al. The limitations of this study include the open-label nature of the study design and the lack of a control placebo arm or a comparator product. The analysis of a drug effect on body weight changes over time by itself is limited because children are expected to grow and gain weight as they age, even during SDX/d-MPH treatment. In addition, some of the subjects who entered this study were not stimulant naive, as some had been previously treated with SDX/d-MPH in the antecedent pivotal study. Thus, previous stimulant exposure may have impacted baseline height and weight measures, resulting in an underestimate of growth velocity changes. | PMC10254966 |
Conclusion | In this study, we show that long-term treatment for up to 1 year with SDX/d-MPH was associated with modest reductions in expected weight and lower-than-expected increases in height, effects that plateaued or diminished later in treatment. Although both weight and height decreased compared with the reference population, the decrease was less than what is clinically significant. | PMC10254966 | ||
Clinical Significance | This phase 3 clinical trial of SDX/d-MPH in children aged 6–12 years showed that the overall effects of SDX/d-MPH on growth velocity were minimal and changes were in a range considered not clinically significant. | PMC10254966 | ||
Acknowledgments | Tiloke | Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Gautam Bijur, PhD, Charlette Tiloke, PhD, and editing support by Kathleen Blake, PhD, all of Ashfield MedComms, an Inizio company, and funded by Corium, LLC. | PMC10254966 | |
Authors' Contributions | All the authors were actively involved in data interpretation, critical review of the data, article writing, and editing. | PMC10254966 | ||
Disclosures | A.C.C serves as consultant for Aadrvark, Arbor, Aytu, Ironshore, Neos Therapeutics, Neurocentria, Noven, Otsuka, Purdue, Rhodes, Sky, Sunovion, Tris Pharma, Zevra Therapeutics (previously KemPharm, Inc.), Supernus, Jazz, Corium, LLC, and Lumos. She has served on the speaker's bureau for Takeda (Shire), Arbor, Ironshore, Neos Therapeutics, Tris Pharma, and Supernus. She has received research support from Allergan, Takeda (Shire), Emalex, Akili, Arbor, Ironshore, Lumos, Neos Therapeutics, Otsuka, Purdue, Adlon, Rhodes, Sunovion, Tris Pharma, Zevra Therapeutics (previously KemPharm, Inc.), Supernus, US Food and Drug Administration, and Servier. She has received writing support from Takeda (Shire), Arbor, Ironshore, Neos Therapeutics, Purdue, Rhodes, Sunovion, and Tris Pharma; She has served on advisory boards for Takeda (Shire), Akili, Arbor, Cingulate, Ironshore, Neos Therapeutics, Neurovance, Otsuka, Purdue, Adlon, Rhodes, Sunovion, Tris Pharma, Supernus, NLS Pharma, and Corium, LLC.A.J.C. is a consultant for AbbVie, Akili Interactive, Arbor Pharmaceuticals, Atentiv, Axsome, Corium, LLC, Ironshore, Neurosigma, Noven, Otsuka, Purdue Canada, Shire, Sunovion, Supernus, Takeda, and Tris Pharma. He has served on speaker's bureaus for AbbVie, Arbor Pharmaceuticals, Axsome, Corium, LLC, Ironshore, Noven, Otsuka, Shire, Sunovion, Supernus, Takeda, and Tris Pharma. He has received research support from Aevi Genomics, Akili Interactive, Arbor Pharmaceuticals, Ironshore, Zevra Therapeutics (previously KemPharm, Inc.), Otsuka, Purdue Canada, Rhodes, Shire, Sunovion, Supernus, and Takeda. He is an employee and board member of the Neuroscience Education Institute.M.P. and C.O. are employees of Corium, LLC. | PMC10254966 | ||
References | PMC10254966 | |||
Background | deaths | Over one million yearly deaths are attributable to | PMC9942299 | |
Methods | human immunodeficiency virus (HIV) infected | We assessed 26 PNSP isolates obtained from the nasopharynx from 537 healthy human immunodeficiency virus (HIV) infected adults in Dar es Salaam, Tanzania, participating in the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890, registered on 23rd March, 2017). Next generation whole genome sequencing on the Illumina platform was used to identify mechanisms of resistance to antibiotics among PNSP. | PMC9942299 | |
Results | Fifty percent (13/26) of PNSP were resistant to erythromycin, of these 54% (7/13) and 46% (6/13) had MLS | PMC9942299 | ||
Conclusion | The | PMC9942299 | ||
Materials and methods | PMC9942299 | |||
Bacterial isolates | Twenty-six penicillin non-susceptible Serotyping of | PMC9942299 | ||
Antimicrobial susceptibility testing | The E-test strip (bioMérieux, Marcy-I-Etoile, France) was used to determine the minimum inhibitory concentrations (MIC) for azithromycin, erythromycin and penicillin. The disk diffusion method was used to determine tetracycline and clindamycin susceptibility [ | PMC9942299 | ||
Whole genome sequencing and analysis | Whole genome sequencing was performed using the Next generation sequencing platform HiSeq X10 (Illumina, San Diego, CA, USA) at MicrobesNG (Microbes NG, Birmingham, UK). Quality filtering and sequencing short read trimming were performed by MicrobesNG using SPAdes and annotated in GenBank. Short read sequences were assembled using Unicycler at MicrobesNG.For allocation of multi-locus sequence typing (MLST) and clonal complex, we used the online MLST database website Identification of acquired resistance was performed using the web-based platform ResFinder v3.2 of the Center for Genomic Epidemiology (For identification of mobile genetic elements and their related acquired antimicrobial resistance we used the Center for Genomic Epidemiology MobileElement Finder v1.0.3 (This Whole Genome Shotgun project has been deposited at DDBJ/ENA/GenBank under the BioProject number PRJNA918594. | PMC9942299 | ||
Statistical analysis | Categorical variables were presented in frequencies, percentages, and proportions. Categorical variables were compared using chi square test. A p-value < 0.05 was considered as threshold for statistical significance. Statistical analysis was performed using STATA version 16 (College Station, TX). | PMC9942299 | ||
Discussion | RESPIRATORY TRACT INFECTIONS, COMMUNITY-ACQUIRED PNEUMONIA | We observed a discrepancy in azithromycin susceptibility depending on whether using breakpoints from EUCAST or CLSI guidelines for interpretation. All 13 PNSP isolates harboring genetic determinants for macrolide resistance were correctly identified as resistant to erythromycin and azithromycin (all with MIC ≥ 4 µg/mL) regardless of which breakpoints were used (sensitivity 100%, 13/13). Using the EUCAST breakpoints appeared to overestimate azithromycin resistance, as all 13 erythromycin-susceptible PNSP without genetic determinants of macrolide resistance were interpreted as resistant to azithromycin (MIC-values from 0.5 to 2, specificity 0%, 0/13). Using CLSI breakpoints only misclassified two such isolates (MIC 2 µg/mL, specificity 85%, 11/13). Therefore, relying on current EUCAST guidelines appears to overestimate azithromycin resistance and could in the clinical perspective lead to unnecessary use of more broad-spectrum antibiotics. Our findings suggest that the EUCAST guidelines currently use a too low cutoff for MIC-values for azithromycin resistance in pneumococci.PNSP susceptibility to erythromycin, on the other hand, was similar using both EUCAST and CLSI breakpoints, and the phenotypic findings correlated well with the identified genotypic resistance markers. To avoid variations in interpretation, our findings call for AST guidelines to be harmonized. Both CLSI and EUCAST state that erythromycin susceptibility can predict susceptibility to clarithromycin, azithromycin, dirithromycin, and roxithromycin [In Tanzania, macrolides are commonly used to treat respiratory tract infections. In the treatment of community-acquired pneumonia, erythromycin and azithromycin are used as first and second line treatment, respectively [The most common phenotype was MLSPrevious studies have shown that tetracycline and macrolide resistance genes are carried on mobile genetic elements, composite conjugative transposons, Tn | PMC9942299 | |
Acknowledgements | Authors thank members of the bacteriology research laboratory of the Muhimbili University of Health and Allied Science in Dar es Salaam, Tanzania, for their assistance during data collection and preliminary laboratory procedures. | PMC9942299 | ||
Author contributions | BB and NL conceived the study. JM collected study data. JM and SM performed the microbiological investigations. BB and JM performed statistical analysis. JM drafted the manuscript. BB, SJM, and NL revised the manuscript. All authors approved the final version. | PMC9942299 | ||
Funding | INFECTIOUS DISEASES | This research was supported by (i) Helse Bergen HF, Haukeland University Hospital, Bergen, Norway, project number 912132, , (ii) National Advisory Unit on Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway, (iii) CAMRIA - Combatting Anti-Microbial Resistance with Interdisciplinary Approaches, Centre for Antimicrobial Resistance in Western Norway, funded by Trond Mohn Stiftelse, grant number TMS2020TMT11, and (iv) STRESST - Antimicrobial Stewardship in Hospitals, Resistance Selection and Transfer in a One Health Context, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, funded by JPIAMR grant number NFR333432. | PMC9942299 | |
Availability of data and materials | Data are available on reasonable request. | PMC9942299 | ||
Declarations | PMC9942299 |
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