Non-randomized Controlled Study Research Articles

A non-randomised controlled study to assess the effectiveness of a new proactive multidisciplinary care intervention for older people living with frailty

Abstract Background Integrated care may improve outcomes for older people living with frailty. We aimed to assess the effectiveness of a new, anticipatory, multidisciplinary care service in improving the wellbeing and quality of life (QoL) of older people living with severe frailty. Methods A community-based non-randomised controlled study. Participants (≥65 years, electronic Frailty Index ≥0.36) received either the new integrated care service plus usual care, or usual care alone. Data collection was at three time points: baseline, 2-4 weeks, and 10-14 weeks. The primary outcome was patient wellbeing (symptoms and other concerns) at 2-4 weeks, measured using the Integrated Palliative care Outcome Scale (IPOS); the secondary outcome was QoL, measured using EQ-5D-5L. To test duration of effect and safety, wellbeing and QoL were also measured at 10-14 weeks. Descriptive statistics were used to characterise and compare intervention and control groups (eligible but had not accessed the new service), with t-test, Chi-Square, or Mann-Whitney U tests (as appropriate) to test differences at each time point. Generalised linear modelling, with propensity score matching, was used for further group comparisons. Data were analysed using STATA v17. Results 199 intervention and 54 control participants were recruited. At baseline, intervention and control groups were similar in age, gender, ethnicity, living status, and body mass index, but not functional status or area deprivation score. At 2-4 weeks, wellbeing had improved in the intervention group but worsened in the control (median IPOS -5 versus 2, p<0.001). QoL improved in the intervention group but was unchanged in the control (median EQ-5D-5L 0.12, versus 0.00, p<0.001). After adjusting for age, gender, and living status, the intervention group had an average total IPOS score reduction at 2-4 weeks of 6.34 (95% CI: -9.01: -4.26, p<0.05); this improvement was sustained, with an average total IPOS score reduction at 10-14 weeks of 6.36 (95% CI: -8.91:-3.80, p<0.05). After propensity score matching based on functional status/area deprivation, modelling showed similar results, with a reduction in IPOS score at 2-4 weeks in the intervention group of 7.88 (95% CI: -12.80: -2.96, p<0.001). Conclusions Our findings suggest that the new, anticipatory, multidisciplinary care service may have improved the overall wellbeing and quality of life of older people living with frailty at 2-4 weeks and the improvement in wellbeing was sustained at three months. Ethics approval NHS Research Ethics Committee 18/YH/0470 and IRAS-250981. Trial registration The trial was retrospectively registered at the International Standard Randomised Controlled Trial Number (ISRCTN) registry (registration date: 01/08/2022, registration number: ISRCTN10613839).

Digital Health Interventions in Patient Management Following Acute Coronary Syndrome: A Meta-Analysis of the Literature.

Acute coronary syndrome patients should be closely followed-up to maintain optimal adherence to medical treatments and to reduce adverse events. Digital health interventions might provide improved outcomes for patient care by providing closer follow- up, compared to standard care. Thus, in this meta-analysis, we aimed to evaluate the effect of digital health interventions on follow-up in acute coronary syndrome patients. We searched medical databases to obtain all relevant studies comparing digital health interventions with standard care in acute coronary syndrome patients. After reviewing all eligible studies, a meta-analysis was conducted with the remaining 11 randomized controlled studies and 2 non-randomized controlled studies. A modified Jadad scale and Newcastle-Ottawa scale were used to assess the quality of the publications for randomized controlled studies and non-randomized controlled studies, respectively. This meta-analysis consisted of 7657 patients. The all-cause mortality rate was 49% lower in the digital health intervention cases, compared to those who received standard care [relative risk (RR) = 0.51 (0.37; 0.70), P <.01]. There was a significant decrease in systolic blood pressure in the digital health interventions group, compared to the standard care group [mean difference = -5.28 (-9.47; -1.08), P =.01]. The rate of nonadherence to anti-aggregant drugs was 69% lower in the digital health interventions than in the standard care group [RR = 0.31 (0.20; 0.46), P <.01]. Also, nonadherence rates for statin and beta-blockers were lower in the digital health interventions group. The risk of rehospitalization was observed to be 55% less in the digital health interventions patients, compared to the standard care group [RR = 0.45 (0.30; 0.67), P <.01]. Digital health interventions can be effective in follow-up for secondary prevention in acute coronary syndrome patients.

Comparison of Clarus and Optomap Ultra-Widefield Imaging Systems before and after EVO-ICL Implantation in High Myopia

Introduction: The aim of this study was to investigate the features of imaging differences between Clarus and Optomap ultra-widefield imaging systems after implantable collamer lens (ICL) implantation. Methods: This was a non-randomized controlled study. Ninety-two eyes of 46 consecutive patients were enrolled. Full-scale ophthalmological examinations were conducted preoperatively. All patients underwent Clarus (CLARUS 500; Carl Zeiss, Dublin, USA) and Optomap (Daytona; Optos, UK) ultra-wide imaging sequentially under the same circumstance preoperatively and 1 month after EVO-ICL implantation. A single image was acquired from each. Dx was defined as the distance between the upper furcation of the central retinal artery and the central fovea of macula. Pixels of the optic cup and disc and Dx as well as the optic cup/disc ratio were calculated and compared on each machine before and after surgery. Results: All surgeries were uneventful without complications. Safety and efficacy indices were both 100% at 1 month. Values of both optic cup and disc areas were in decrease after surgery with statistically significant differences (p < 0.001), while the cup/disc ratio remained the same (Clarus mean of differences = −0.0028, p = 0.83; Optomap mean of differences = −0.0016, p = 0.76). Dx of images captured with either machine was statistically significantly decreased (p < 0.001). Differences of both optic cup (p = 0.057) and disc (p = 0.041) areas of Clarus were more obvious than that of Optomap, while only the latter was with statistical significance. Difference of Dx of Clarus was statistically significantly larger than Optomap. Conclusions: Display ranges tend to be broadened after EVO-ICL implantation in both Clarus and Optomap ultra-widefield imaging systems, while Clarus shows a wider display range of the two, which encourages the application of Clarus when it comes to the detection of more peripheral retinal lesions.

Baby Finger Toothbrush as an Innovative Alternative for Finger Method of Teeth Cleaning to Improve Oral Hygiene in Rural India

Background: Most of the rural Indian population cleans the teeth with their finger and they find it difficult to switch to a manual toothbrush. To continue their legacy of cleaning the teeth with their finger, we conducted a study with a baby finger toothbrush, which is used by inserting an index finger for brushing the baby’s teeth. Objective: The objective of this study was to compare the efficacy of a baby finger toothbrush with teeth cleaning method using finger. Materials and Methods: Sixty adults who cleaned their teeth with their fingers were divided into two groups. Those participants who were willing to use baby finger toothbrushes were included in Group A and the remaining participants were part of Group B. A nonrandomized controlled trial study design was used. Group A Participants were asked to use baby finger toothbrushes for 15 days. The oral hygiene index-simplified (OHI-S) was recorded for both the groups on day 1 and after 15 days. We then compared the oral hygiene status for those who use baby finger toothbrush with those who clean the teeth using finger. Results: OHI-S was significantly higher in the participants cleaning teeth with their fingers compared to the participants using baby finger toothbrush after 15 days. It showed that using a baby finger toothbrush is more effective than using your fingers to improve oral hygiene. Participants who used the baby finger toothbrush had the median OHI-S of 1.33, which is close to a good OHI-S (good-OHI-S = 0.0–1.2) and indicates that baby finger toothbrush was able to maintain “Fair” oral hygiene. Conclusion: To improve oral hygiene in rural India, where most individuals clean teeth with their fingers, a baby finger toothbrush can be used as an improvised method of tooth cleaning.

Effect of Different Occlusal Tooth Forms of Mandibular Overdenture Retained by an Immediate Loaded Single Implant on the Masticatory Efficiency and Oral Health-Related Quality of Life.

To study the masticatory efficacy and oral health-related quality of life (OHRQoL) of participants wearing a mandibular overdenture retained by an immediate loading single implant with different occlusal tooth forms. For this nonrandomized controlled trial study, 27 edentulous participants were selected and randomly divided into three groups (n = 9) based on occlusal tooth forms of the mandibular implant overdenture (MIOD). Group I: participants received an MIOD with an anatomical tooth form; Group II: participants received an MIOD with a semianatomical tooth form; and Group III: participants received an MIOD with a nonanatomical tooth form. For each participant, a single implant (screw root form) was inserted into the midline of the mandibular ridge to support the MIOD. For each group, the masticatory efficiency was evaluated after 3 months, and the OHRQoL of the participants was evaluated after 3 and 6 months. One-way ANOVA and post hoc Tukey's test were used for data analysis (P < 0.05). The masticatory efficiency of the anatomic and semianatomic tooth forms was higher than that of the nonanatomic (P < 0.05). Moreover, the improvement in the participants' OHRQoL in the anatomic group was more significant than that of other groups (P < 0.05). There was a greater improvement in masticatory efficiency and participants' OHRQoL when fitted with an anatomic tooth form mandibular overdenture retained by an immediate loading single implant than with a semianatomic or nonanatomic tooth form.

Comparative Study Between Pedicled Latissimusdorsi Flap Reconstruction And Traditional Conservative Breast Surgery in Upper Outer Quadrant Breast Cancer

Background:Oncoplastic breast surgery (OPS)has developed as an extension of breast conserving surgery (BCS) in an effort to improve esthetic and functional outcome following surgery for breast cancer (BC). This study evaluatedthe benefits of reconstruction using the latissimusdorsi(LD) flap, as compared with local tissue displacement.Methods: This was a comparative non-randomized control study on patients after excision of the malignant mass from the upper outer quadrant BC. The two groups were classified into Group A: reconstruction by local tissues displacement, and Group B: reconstruction by pedicledLD flap.The two techniques were compared regarding history, examination finding, intraoperative and post-operative complications.Results:there was no significant difference between group A and B regarding their age, BMI, distance between tumor, NACandpostoperative complications. Tumor size was larger in group B,there was a significant longer operative time,increased blood loss and longer time to recoveryin group B than group A.Conclusion: OPS with breast reconstruction using the pedicledLD flap accompanied with better intra and postoperative outcomes.

Bone Turnover Markers Changes Induced by Plateletpheresis May Be Minimized with Oral Supplementation of Calcium, Minerals, and Vitamin D before the Procedures: A Non-Randomized, Controlled Study.

Apheresis allows the collection of specific blood components but changes serum calcium (Ca), magnesium (Mg), copper (Cu), zinc (Zn), and hormones involved in bone metabolism due to citrate infusion. We assessed the effect of oral supplementation of calcium, vitamin D, and minerals as pills or an enriched diet before plateletpheresis donation on levels of divalent cations, hormones, and bone turnover markers that may prevent metabolic changes. Methods: Non-randomized controlled study including 134 donors. Serum parathyroid hormone (PTH), Ca, Mg, Zn, Cu, osteocalcin (OC), vitamin D, and type-1 collagen C-terminal telopeptide (CTX-1) levels were measured at baseline and post-procedure. Donors were divided into four groups: supplemented with calcium carbonate and vitamin D (cal + vitd); those receiving calcium, minerals, and vitamin D (cal + vitd + min); those receiving a calcium-rich diet (diet) and a control group (control). Results: PTH levels increased >1-fold, whereas tCa, tMg, Zn, Cu, iCa, iMg, and vitamin D levels decreased immediately after apheresis amongst donors of any group; when these levels were measured two weeks later, donors in the calcium-vitd and cal + vitd + min groups returned to basal values; donors in the cal + vitd + min group were the only group that kept their levels of OC and CTX unchanged at the different study times. Conclusions: Bone turnover markers changes induced by plateletpheresis may be minimized with oral supplementation of calcium, minerals, and vitamin D two days before the procedures.

Management of Children with Speech Disorders via Transcranial Magnetic Stimulation: Non-Randomized Controlled Study

Background. Speech development impairment is urgent and common problem in pediatric neurology. Transcranial magnetic stimulation (TMS) is one of the promising treatment variants for children with speech disorders. Objective. The aim of the study is to evaluate efficacy and safety of the developed approaches to TMS usage in the management of children with speech disorders. Methods. It was non-randomized controlled study. It included 46 children with speech disorders aged from 3 to 6.5 years. All children were divided into two groups comparable by gender and age: 26 children of the treatment group received TMS course, 20 children of the control group received treatment with hopantenic acid. All patients with speech disorders underwent psychological and pedagogical evaluation of speech and cognitive development, electroencephalography (EEG) before and after treatment. Moreover, comparative analysis of TMS and nootropic therapy efficacy was carried out. Specialized examination of speech and cognitive development was also performed via E.A. Strebeleva method for psychological and pedagogical diagnosis of children development. Furthermore, we carried out side reactions / adverse events registration according to patients and/or their parents complaints confirmed by physical examination, patient’s behavior observation, data from specially developed questionnaire for assessing child’s behavior and well-being (filled up by parents). Finally, we evaluated brain bioelectric activity recorded by EEG. Results. The study results have shown that it is possible to achieve significant positive dynamics in cognitive and speech development in preschool children with speech disorders in both groups (TMS course and medical treatment). But hereby, TMS treatment has demonstrated significantly higher positive dynamics in two out of the three evaluated parameters. There were no cases of adverse events in TMS group leading to early course discontinuation. Conclusion. TMS is non-invasive and safe method for treatment of children with speech disorders. This study has demonstrated the efficacy of the method in the field of personalized management of children with impaired speech and cognitive development.

Effect of psychosocial interventions on risky driving behaviours among offender drivers by using simulated and real driving: study protocol for a non-randomised controlled trial

BackgroundRisky driving behaviour including anger while driving has led to millions of global road traffic crashes, thousands of mortalities and injuries. These losses are much more in middle-income countries, such...

Meta-Analysis of Effectiveness and Safety of Botulinum Toxin in the Treatment of Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is characterized by pain, limited range of motion, swelling, skin changes, vasomotor instability, and patchy bone demineralization. Conservative management strategies for CRPS include physical and occupational therapy, psychosocial and behavioral therapy, and pharmacotherapy. However, some patients still experience CRPS symptoms after receiving conventional treatments. Therefore, botulinum toxin (BoNT) has been applied to patients with CRPS in several trials considering its analgesic effect in musculoskeletal and neuropathic pain; however, the results were controversial. We conducted the study to explore the effectiveness and safety of BoNT in patients with complex regional pain syndrome (CRPS). A search was performed using the following electronic databases up to 19 October 2022: PubMed, Embase, and Cochrane Library. We included both randomized controlled trials and nonrandomized controlled studies involving patients with complex regional pain syndrome managed with botulinum toxin. Cochrane risk-of-bias tool and Joanna Briggs Institute Critical Appraisal Checklist were used for quality assessment for randomized controlled trials and quasi-experimental studies. Only randomized controlled trials entered the meta-analysis. The primary outcome was the visual analogue scale of pain presented as a weighted mean difference (WMD) and 95% confidence interval (CI). The secondary outcome was the risk of adverse events presented as an odds ratio (OR) with 95% CI. We analyzed eight articles with 176 patients, including three randomized controlled trials with 62 participants. The age of the patients ranged from 23.8 to 51 years old. The duration of the disease ranged from 2.2 to 11.8 years. The proportion of females ranged from 16.6% to 100%. The route of administration of BoNT included: (1) lumbar sympathetic block (LSB), (2) intramuscular injection, (3) subcutaneous or intradermal injection (SC/ID). Improvement in pain was revealed in six studies, and adverse events were all self-limited and temporary. Meta-analysis revealed a significant reduction in pain at the first follow-up between 3 weeks to 1 month after intervention (WMD, -1.036, 95% CI, -1.673 to -0.400) but not at the second follow-up between 2 to 3 months after treatment (WMD, -0.895, 95% CI, -2.249 to 0.458). Subgroup analyses between LSB and SC/ID were nonsignificant at both follow-up periods (p = 0.422, 0.139). The risk of adverse events was similar between the BoNT and control group (OR, 0.698, 95% CI, 0.136 to 3.581). In conclusion, BoNT may be effective and safe for alleviating pain in patients with CRPS. However, we could not draw definite conclusions due to small sample size and high between-study heterogeneity. The limited number of participants may conceal the possibility of serious adverse events. Further large-scale randomized controlled trials are warranted to delineate the role of BoNT in CRPS.

Virtual and Augmented Reality versus Traditional Methods for Teaching Physiotherapy: A Systematic Review.

The use of virtual worlds in health-related education is increasingly popular, but an overview of their use in physiotherapy education is still needed. The aim of this review was to analyse the use of virtual and augmented reality (VR/AR) compared to traditional methods for teaching physiotherapy. A systematic review was performed up to October 2022 in PubMed, Web of Science, Scopus, CINAHL, and PsycInfo. The quality appraisal and risk of bias were assessed by the Joana Briggs Institute checklist and the Cochrane Collaboration's RoB Tool 2.0, respectively. A total of seven randomised and non-randomised controlled studies were included, involving 737 students. VR/AR-based teaching approaches included simulation and virtual worlds, and were conducted through immersive head-mounted displays, AR-based applications, and 3D visualisations. Three studies were focused on teaching anatomy content, two on clinical decision making skills, and the rest were focused on pathology, physiotherapy tasks or exercise performance, and movement analysis of lower limbs. Inconclusive results were found in terms of learning satisfaction and academic performance, showing VR/AR-based teaching models to be equally effective as traditional methods for teaching physiotherapy. We encourage researchers and teachers to include games in their VR/AR-based teaching approaches to enhance interaction and active learning in physiotherapy education.

Acupuncture for Adult Obstructive Sleep Apnea or Obstructive Sleep Apnea-Hypopnea Syndrome: A Review of the China National Knowledge Infrastructure Database

The purpose of this study was to analyze acupuncture treatment methods and acupoints used to treat obstructive sleep apnea (OSA) or obstructive sleep apnea-hypoapnea syndrome (OSAHS). The data were retrieved from January 2010 to May 2022 from the China National Knowledge Infrastructure database. The search terms included “adult,” “obstructive sleep apnea,” “obstructive sleep apnea hypoapnea syndrome,” “acupuncture,” and “electro-acupuncture.” Clinical trials for acupuncture treatment of OSA or OSAHS were included in this review (4 non-randomized controlled studies, 1 was a case report, and 10 randomized controlled studies). For OSA and OSAHS treatment, the acupoints that were most frequently used included REN23, LU7, ST40, EX9, LI11, and DU20. Compared with the control or Western treatment group, the treatment outcome measures of participants in the acupuncture treatment group significantly improved. In some studies, participants in the acupuncture group did not have side effects and the treatment was cost-effective. The data analyzed in this review suggest that acupuncture is an effective treatment for OSA or OSAHS.

Immediate versus delayed implant placement in the esthetic zone: a prospective 3D volumetric assessment of peri-implant tissue stability

PurposeTo evaluate the volumetric stability of peri-implant soft and hard tissue prospectively, this study compared immediate versus delayed implants placed in the anterior esthetic region.MethodsThis non-randomized controlled clinical study included 25 patients, who received an immediate (type 1) or a delayed (type 4) implant placement for the replacement of a single anterior tooth. The anterior maxillae were intraorally scanned at three timepoints: before surgery (S0), 6 months (S1), and 12 months (S2) after surgery. A specific region of interest (ROI), divided into marginal and apical regions, was determined and superimposed for volumetric changes analysis. At 6 and 12 months, the probing depth (PD), bleeding/suppuration on probing (BOP/SUP), modified plaque index (PI), keratinized mucosa (KM) width, mucosal recession (MR), and implant stability (PTV) by means of periotest were recorded.ResultsBetween S0–S2, tissue surrounding immediate implants was reduced in 0.37 ± 0.31 mm, whereas delayed implants gained 0.84 ± 0.57 mm mean tissue volume. Peri-implant tissue loss at type 1 implants occurred primarily in the marginal section of the ROI (0.42 ± 0.31 mm), whereas tissue gain at type 4 implants occurred mainly in the apical section (0.83 ± 0.51 mm). These values were significantly different between both groups for the entire ROI (p = 0.0452) and the marginal region (p = 0.0274). In addition, the mean buccal KM width around type 1 implants was significantly wider in comparison with the type 4 implants group after 12 months (p = 0.046). There were no significant differences between groups regarding PD, BOP/SUP, or PTV.ConclusionsThe results suggest that type 1 implants placed in the esthetic region experience more tissue loss than type 4 implants, thus marginal tissue remodeling should be considered for planning immediate implants placement in the anterior maxillae.Graphical

The links between adipose tissue DNA methylation, obesity, and insulin resistance: A protocol for systematic review.

Obesity is a metabolic condition brought on by the interplay of hereditary and environmental factors, making it one of the most common diseases in the world. Insulin resistance (IR) and obesity have a close connection and can both be advantageous. One of the main methods of epigenetic regulation is DNA methylation modification. Studies have demonstrated over the past few years that DNA methylation is crucial to the emergence of obesity and DNA methylation can lead to IR. Adipose tissue participates in the physiopathological processes of obesity and IR and functions as an endocrine organ controlling the body's balanced metabolism, thus, adipose tissue-associated gene DNA methylation affects the development of obesity and IR by influencing the function of adipose tissue. Hence, an explanation of current research on DNA methylation, IR, and obesity, following the most recent developments, exploring changes in DNA methylation in different types of adipose tissue in insulin-resistant patients and obese patients may enable the identification of novel targets in clinical obesity prevention and treatment. The following electronic bibliographic databases will be searched from inception for peer-reviewed original research published: MEDLINE (through PubMed), Scopus, and EMBASE. Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform from inception to December 31, 2021 will be conducted. Systematic reviews will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. The development of search strategies will make use of medical issue phrases and keywords associated with DNA methylation, Adipose tissue DNA methylation, obesity, and IR. Identified citations will be independently reviewed by two authors to determine eligibility at the title and abstract level, and then at the full text and data extraction phases. Disagreements and conflicts will be resolved through discussion with a third author. Two authors will extract the necessary data from the included studies independently, and The Cochrane Risk of Bias Assessment Tool will be used to assess the bias of randomized controlled studies, and the Newcastle-Ottawa scale for nonrandomized controlled studies. If the interventions and outcomes evaluated are sufficiently homogeneous, results from subgroups of studies will be pooled together in a meta-analysis.

Effect of Experiential Communication Skills Education on Graduate Medical Education Trainees' Communication Behaviors: A Systematic Review.

A better understanding of how communication skills education impacts trainees' communication skills is important for continual improvement in graduate medical education (GME). Guided by the Kirkpatrick Model, this review focused on studies that measured communication skills in either simulated or clinical settings. The aim of this systematic review was to examine the effect of experiential communication skills education on GME trainees' communication behaviors. Five databases were searched for studies published between 2001 and 2021 using terms representing the concepts of medical trainees, communication, training, and skills and/or behaviors. Included studies had an intervention design, focused only on GME trainees as learners, used experiential methods, and had an outcome measure of communication skills behavior that was assessed by a simulated or standardized patient (SP), patient, family member, or outside observer. Studies were examined for differences in outcomes based on study design; simulated versus clinical evaluation setting; outside observer versus SP, patient, or family member evaluator; and length of training. Seventy-seven studies were ultimately included. Overall, 54 (70%) studies reported some positive findings (i.e., change in behavior). There were 44 (57%) single-group pre-post studies, 13 (17%) nonrandomized control studies, and 20 (26%) randomized control studies. Positive findings were frequent in single-group designs (80%) and were likely in nonrandomized (62%) and randomized (55%) control trials. Positive findings were likely in studies evaluating communication behavior in simulated (67%) and clinical (78%) settings as well as in studies with outside observer (63%) and SP, patient, and family member (64%) evaluators. This review demonstrates strong support that experiential communication skills education can impact GME trainees' communication behaviors. Marked heterogeneity in communication trainings and evaluation measures, even among subgroups, did not allow for meta-analysis or comparative efficacy evaluation of different studies. Future studies would benefit from homogeneity in curricular and evaluation measures.

Intermittent Use of Anti-Hormonal Agents for the Endocrine Therapy of Sex-Hormone-Dependent Breast and Prostate Cancer: A Protocol for a Systematic Review.

Therapies with the continuous administration of anti-hormonal agents in sex-hormone-dependent malignancies such as prostate and breast carcinomas often lead to the development of resistant tumor cells. A systematic evaluation of the use and effects of the intermittent application of endocrine therapy could provide information on the state of knowledge in this research area. PubMed, Cochrane Library, Embase, and Web of Science will be systematically searched using pretested search strategies. Randomized and non-randomized controlled trials, pragmatic trials, case-control, and comparative cohort studies will be eligible. Primary outcomes will be progression-free survival, disease-free survival, and overall survival. The literature retrieved will be selected based on predefined inclusion and exclusion criteria. Relevant data will be extracted from included references into a pre-designed table. The risk of bias will be assessed, and the report of the results will follow PRISMA recommendations and include any deviations from this protocol. The increasing prevalence of breast and prostate cancer and limitations of current therapeutic approaches require a closer look at alternatives. Additionally, to explore new therapeutic agents, modalities of administration should be rigorously reviewed to determine the best regimens for patients. This proposed systematic review aims to summarize and evaluate the current knowledge regarding intermittent endocrine cancer therapy to provide a basis for further research.

The effect of emergency department pharmacists on drug overuse and drug underuse in patients with an ADE-related hospitalisation: a controlled intervention study

BackgroundDrug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit.MethodsA multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group.ResultsA total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039).ConclusionEmergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit.

A Systematic Review of Omega-3 Fatty Acid Consumption and Cognitive Outcomes in Neurodevelopment.

This systematic review addresses the effects of n-3 long-chain polyunsaturated fatty acids consumption on human neurodevelopment. It evaluates articles published between 2000 and 2022 investigating the cognitive outcomes during the period of neurodevelopment: from fetal development to adolescence. For the purpose of this review the terms LC PUFA and omega-3 fatty acid will be used interchangeably. Data were sourced from several major databases including PubMed (MEDLINE), Web of Science, and ProQuest Central. Randomized controlled trials (RCTs), nonrandomized controlled trials, prospective or retrospective cohort studies, and observational studies investigating the effects of omega-3 fatty acid consumption from dietary supplements, multiple-nutrient supplement, or food questionnaire on neurodevelopment were considered. Study population was separated in three developmental phases: (1) in-utero, (2) lactation/infancy, and (3) childhood/adolescence. Each article was evaluated for several key factors such as study type, type/dosage of PUFAs, number of subjects, length of intervention, participant age range, population characteristics, outcome measure (both primary/cognitive and secondary/other), results, conclusion, and confounding variables/limitations. A total of 88 articles were included in the review, 69 RCTs and 19 longitudinal or observational studies. The results indicate equivocal effect of intervention, with some short-term benefits observed in the areas of visual attention, working memory, executive function, and communication. Omega-3 supplement might have a short-term positive impact on neurodevelopment in all three phases. Supplementation is recommended throughout life, rather than only during the earliest developmental stage.

Ixazomib, Lenalidomide, and Dexamethasone (IRd) Versus Ixazomib, Pegylated Liposomal Adriamycin, and Dexamethasone(IDd) in Elderly Frail Newly Diagnosed Multiple Myeloma with GA Score ≥2: A Prospective Multicenter Study

Introduction Frailty patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and higher rate of treatment discontinuation due to complications, poor tolerance and compliance and lack of effective treatment. The aim of this study was to prospectively investigate the treatment tolerability, clinical outcomes and quality of life of the ixazomib based regimens in frail NDMM patients according to IMWG frailty index. This trail is registered at http://www.chictr.org.cn/index.aspx as chiCTR1900024917. Methods This prospective trail was an investigator initiate, multicenter, non-randomized controlled study which frail NDMM patients received 6-8 four-week induction cycles of ixazomib, lenalidomide and dexamethasone (IRd) and ixazomib, pegylated liposome adriamycin and dexamethasone (IDd), followed by matienance therapy of 4-week with ixazomib and dexamethasone (Id) until progression. Inclusion criteria were aged ≥ 65 years, IMWG GA score ≥ 2 or Mayo geriatric vulnerability scoring system defined as vulnerable. Main exclusion criteria were acute cardiovascular and cerebrovascular events. The primary endpoint was overall response rate (ORR) defined by having at least a partial response (≥PR). The secondary endpoints were progression free survival (PFS), overall survival (OS), adverse events (AE) and health-related quality of life (using the EORTC-QLQ C30). Results From July 2019 to December 2021, a total of 132 patients from 15 hospitals were enrolled of which 12 were excluded because of ineligibility and non-randomized assigned to receive IRd group (n=60) or IDd (n=60) according to doctor's estimated (Figure 1). The median age was 71 years range (65-88). All patients had a GA Index higher than 2 score, in which 27.5% were also defined fragile by Mayo criterion. The ORR was 83%, including 22 (19.6%) patients with a complete response (CR) and 45 (40.2%) with a very good partial response (VGPR). The ORR was 84.2% and 81.8%, CR was 26.3% and 17.2, VGPR was 36.8% and 43.6% of IRd and IAd group, respectively. After a median follow-up time of 22.9m (95% CI 18.9-26.9), the median PFS was 19.5m of all patients, 24.6m and 15.8 of IRd and IDd group, respectively. The median OS of all patients and IRd group was no reach, while 29.2m in IDd group (Figure 1). Four patients died in 60 days post enroll up because of pneumonia caused by bedridden. Twenty-six and thirty-six patients did not process to maintenance therapy in IRd and IAd group, due to PD (14 in IRd and 16 in IDd), AE (6 in IRd and 7 in IDd), incompliance (5 in IRd and 9 in IDd) and early death (1 in IRd and 3 in IDd). Cumulative grade 3 or higher hematological AEs occurred in 10/60 (16.7%) and 13/60 (21.7%), whereas grade ≥3 non-hematological AEs were reported in 25/60 (41.7%) and 46/60 (76.6%) patients. Most common non-hematological grade ≥3 AEs were infections (20.8%) and gastro-intestinal (13.3%). Only 1 patient experiencing PNP grade 3 (0.83%). During induction, patients experienced a statistically and clinically significant improvement in GHS/QoL of both IRd and IAd group (p<0.0001). (Figure 1) Conclusion The results of ORR and safety support the use of IDd or IRd as frontline therapy for fragile elderly MM patients, which also improves QoL. IDd was especially suitable for frail MM patients with renal dysfunction and thrombosis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effect of sodium-glucose cotransporter-2 inhibitors on aldosterone and renin levels in diabetes mellitus type 2 patients: a systematic review and meta-analysis

The effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on plasma aldosterone concentration (PAC) and plasma renin activity (PRA) levels are still inconclusive. This meta-analysis aimed to demonstrate the changes in PAC and PRA levels after the use of SGLT2i in type 2 diabetes patients. A search for relevant publications was performed using PubMed/Medline, Scopus, Cochrane, and Embase databases from their inception through May 2022. Inclusion criteria were studies that contained data on crude PAC and PRA levels before and after the use of SGLT2i in adult type 2 diabetes patients. Standardized mean difference (SMD) with a 95% confidence interval (95% CI) was calculated. Data was separately analyzed by study design: randomized controlled study (RCT) and non-randomized controlled study (non-RCT). Ten studies involving 380 patients were included with two RCT and eight non-RCT. Serum PAC levels showed no significant change after the use of SGLT2i in both RCT and non-RCT. Significantly higher PRA levels were observed after the use of SGLT2i in both RCT and non-RCT with SMD of 0.40 ng/mL/hr; 95% CI (0.06, 0.74) and SMD of 0.36 ng/mL/hr; 95%CI (0.17, 0.55), respectively. Subgroup analysis found significantly higher PRA levels after the use of SGLT2i (SMD 0.45 ng/mL/hr; 95% CI (0.18, 0.71)) only in subgroups that used for three months or less. The use of SGLT2i in diabetes mellitus type 2 patients can affect PRA levels, especially during short-term use. PRA levels should be interpreted with caution in this population.