Objective: To investigate the association between cesarean delivery (CD) and trajectory patterns of age- and sex-specific body mass index (BMI) z-score in early childhood.Methods: A retrospective cohort study was conducted among 2,685 children whose maternal age at the time of birth was between 18 and 35 years, and birth data and anthropometric measurement data during their ages 3–60 months were collected. A group-based trajectory modeling approach was used to identify distinct BMI z-score trajectories, and multinomial logistic regressions were applied to estimate the associations among CD (both elective and non-elective combined), elective and non-selective CD, and BMI z-score trajectory classes.Results: Of the 2,685 participants, 46.5%  were born by vaginal delivery (VD), 20.7% (N = 556) by elective CD, and 32.8% (N = 881) by non-elective CD. Five BMI z-score trajectory patterns were identified, and they were “increasing from moderate to high” , “increasing from mild to moderate” , “increasing from low to high” , “stable mild” , and “stable low”  groups. Compared with children delivered by VD, those who delivered by CD (both elective and non-elective combined), elective CD, and non-elective CD were associated with the “increasing from moderate to high” trajectory  and were also associated with the “increasing from low to high” trajectory .Conclusion: Both elective and non-elective CD were associated with the risk of accelerated weight gain in early childhood. The cesarean delivery (CD) rate has increased significantly in the past decades worldwide . RankingChildhood overweight and obesity have become a global public health concern, and numerous studies have shown that there is a distinct rise in overweight and obesity prevalence in both urban and rural regions of China . ChildhoSome studies have investigated the association between CD and childhood obesity. Although some studies have reported that CD is significantly associated with risk of childhood overweight/obesity or higher body mass index (BMI) –15, heteIn response to these literature gaps, we designed a retrospective cohort study to investigate the association between CD as well as its subtypes (elective and non-elective CD) and trajectory patterns of age- and sex-specific BMI z-score in children aged 3–60 months, which could overcome the limitation of static analysis and increase comparability across ages.http://www.nbphsp.org.cn/jbgw/06rt/), which was launched by the Chinese government in 2009. In this project, one of the nine service categories was providing health services for Chinese children aged 0–6 years for free, including the establishment of maternal and children health records, post-partum visits, physical examinations, and health consultation. Health providers involved in this project were all trained according to national standards and required to provide elaborate health services for children who were at ages of 3, 6, 8, 12, 18, 24, 30, 36, 48, 60, and 72 months.We designed this retrospective cohort study in Huangdao Maternal and Child Health Care Hospital, which provides prenatal care, delivery, postnatal, and child health care service for all residents in Huangdao district, Qingdao, China. This study is based on the National Basic Public Health Service Project  offspring with missing covariate data. The study was conducted in accordance with the Declaration of Helsinki, and the protocol and the use of the database were approved by the Ethics Committee of the Huangdao Maternal and Child Health Care Hospital.Participants were singleton offspring born at term in this hospital between January 1, 2012, and December 31, 2013, and had height/length and weight repeatedly measured 4 to 10 times during the following 5 years. Inclusion criteria were (1) singleton offspring born with 37–42 completed weeks of gestation and (2) mother's age at birth between 18 and 35 years. Exclusion criteria were (1) mothers who were already diagnosed with types 1 or 2 diabetes before the index pregnancy or (2) offspring conceived by Delivery mode  data and the following individual-level covariates were collected from the birth records: maternal age at birth, maternal education level, parity, hypertensive disorders of pregnancy, gestational diabetes mellitus, gestational age at birth, and birth weight. Maternal BMI was measured at the first prenatal visit, and BMI status was defined by using Asian BMI cut points  .Age- and sex-specific BMI z-score trajectory patterns were the outcomes of interest, and anthropometric measurements were performed by trained health providers for participants dressed in light indoor clothing without shoes. Recumbent length for children aged <24 months and standing height for children aged ≥24 months were measured to the nearest 0.1 cm with an infantometer and a stadiometer, respectively. Body weight was measured to the nearest 0.1 kg using a digital scale. All of the instruments were calibrated before measuring, and both length/height and weight were measured twice; then, the mean values were recorded. BMI was calculated as weight (kilogram) divided by height/length (square meter), and age- and sex-specific BMI z-score was calculated using the “igrowup”package for SAS based on World Health Organization Child Growth Standards .A group-based trajectory modeling approach was applied to identify trajectories of BMI z-score from aged 3 months through 60 months. This approach has been widely used in other childhood populations across longitudinal data to identify several discrete classes and individuals in each class following similar trends of change . To fullDifferences in maternal and offspring characteristics among the identified BMI z-score trajectory groups were examined using one-way analysis of variance or chi-square-test. To examine the association between delivery mode and BMI z-score trajectory patterns, crude and adjusted multinomial logistic regression models were used to report OR with 95% CI. We constructed three models: model 1 was the crude model, model 2 adjusted for gestational age at birth and birth weight, and model 3 adjusted for gestational age at birth, birth weight, maternal age at birth, maternal education level, maternal BMI at the first prenatal visit, parity, hypertensive disorders of pregnancy, and gestational diabetes mellitus. We further conducted a stratification analysis by child sex to test whether there is a sex-specific effect on BMI z-score trajectory patterns. All statistical analyses were conducted using SAS version 9.4 .N = 1,248) of the children were born by VD, 20.7% (N = 556) by elective CD, and 32.8% (N = 881) by non-elective CD. The mean maternal age at birth was 28.2 years, and the prevalence of maternal obesity/overweight was 29.8%. In addition, 52.3%  of the children were boys, and the mean gestational age and birth weight were 39.1 weeks and 3.06 kg, respectively. We compared the characteristics of the excluded children and the children having <4 anthropometric measures with the characteristics of the included children, respectively , “increasing from mild to moderate” , “increasing from low to high” , “stable mild” , and “stable low”  groups. Among the five groups, significant differences in proportions of delivery mode, maternal BMI status, maternal education level, gestational diabetes mellitus, parity, offspring sex, and means of gestational age and birth weight were observed (Children had a median of six repeated anthropometric measurements (interquartile range: 5–8 times) from 3 to 60 months of age. Numbers of children who had anthropometric measurements at the age of 3, 6, 8, 12, 18, 24, 30, 36, 48, and 60 months were 2,136, 2,029, 1,767, 1,938, 1,713, 1,725, 1,608, 1,627, 1,534, and 1,489, respectively. The five-group model proved optimal for describing BMI z-score trajectory patterns from age 3 months through 60 months . We labeobserved .In the unadjusted model, compared with children delivered by VD, those who delivered by CD were significantly associated with the two trajectories characterized by accelerated BMI z-score gain , and results were similar for both elective and non-elective CD . In addiIn this retrospective cohort study, we identified five distinct BMI z-score trajectories during early childhood and found significant associations of CD and its subtypes with two trajectories characterized by accelerated BMI z-score gain. Our findings suggest that newborns delivered by CD, irrespective of subtypes, would have an accelerated weight growth pattern during early childhood. To the best of our knowledge, this is the first study to explore the association between delivery mode and BMI z-score trajectory patterns during early childhood. This study provides new insights into the origins of overweight and obesity in early childhood life and emphasizes the importance of reducing the overused cesarean section.In this population, the prevalence of maternal obesity/overweight is 29.8%, which is similar to the prevalence of obesity/overweight in women aged 20–39 years from the 2011 China Health and Nutrition Survey 26.3%) . A total.3% . A tOur association analyses showed that children delivered by CD were associated with an increased risk of having trajectories characterized by accelerated weight gain, although the effect estimates attenuated distinctly after adjustment for maternal and offspring variables. This result is similar to previous studies reporting positive associations between CD and larger childhood BMI or risk of overweight/obesity –15. HoweWith regard to the effects of different subtypes of the CD on offspring overweight and obesity, existing studies also showed discordant findings. Both elective and non-elective CDs were found to be associated with obesity in children aged 3–6 years from China  and in cThe group-based trajectory modeling approach in our study makes it possible to explore the potential heterogeneity of BMI z-score changes during early childhood, which is an essential difference against the studies mentioned earlier. Several previous studies have identified the role of stable high BMI or rapid BMI gain during childhood contributing to increased risk for obesity in adulthood, suggesting the potential ability of childhood BMI trajectories in predicting health outcomes in later life , 31. TheThe exact mechanisms of CD leading to obesity or accelerated BMI gain during childhood is still unclear, but alterations in the gut microbiota via different delivery modes are a potential biological mechanism speculated by many researchers. The fetus and the intrauterine environments are believed to be sterile, and thus, the intestinal microbiome developed beginning at birth may be dependent on whether the newborn's first contact was with the vaginal canal or skin microbiota . SeveralThis study has several strengths. The retrospective cohort design with sufficient repeated anthropometric measurements and the group-based trajectory modeling approach enabled us to classify children into diverse growth trajectories. Besides, BMI z-score other than BMI was used to model the growth trajectory, which allowed for estimating how individuals tracked according to their rank order within BMI distributions and exempting the need for age and sex adjustment and also providing the most meaningful measure to investigate the relationship between delivery mode and change in weight status .First, the development of obesity in childhood is a multifactorial phenomenon, but data on some confounding factors, such as maternal passive smoking, maternal breastfeeding pattern, child daily diet structure, physical and sedentary activity, and family income level, are absent in this study , 37, 38.The control of CD rate, especially the elective CD rate, should be considered as a priority goal for reducing childhood obesity and subsequently decreasing the risk of cardiovascular and metabolic diseases in later life. Communities, antenatal care sections, and hospitals should promote effective health education for pregnant women.jiaxiao2019@163.com.The data analyzed in this study is subject to the following licenses/restrictions: The data underlying the study are not available to the public as the project does not meet the budget requiring data sharing. Requests to access these datasets should be directed to Xiao Jia, The studies involving human participants were reviewed and approved by The Ethics Committee of the Huangdao Maternal and Child Health Care Hospital.LZ, WQ, and XJ conceptualized the study and drafted the article. LZ, LH, and RD collected all data with initial pre-processing. HL, ZZ, and LZ analyzed data. ZZ and LZ also made contributions to revising the manuscript. All authors approved the final submitted and published versions.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Previous studies have shown that influenza is associated with a substantial healthcare burden in the United Kingdom (UK), but more studies are needed to evaluate the resource use and direct medical costs of influenza in primary care and secondary care.A retrospective observational database study in the UK to describe the primary care and directly-associated secondary care resource use, and direct medical costs of acute respiratory illness (ARI), according to age, and risk status (NCT Number: 01521416). Patients with influenza, ARI or influenza-related respiratory infections during 9 consecutive pre-pandemic influenza peak seasons were identified by READ codes in the linked Clinical Practice Research Datalink (CPRD) and Hospital Episodes Statistics (HES) dataset. The study period was from 21st January 2001 to 31st March 2009.A total of 156,193 patients had ≥1 general practitioner (GP) episode of ARI, and a total of 82,204 patients received ≥1 GP prescription, at a mean of 2.5 (standard deviation [SD]: 3.0) prescriptions per patient. The total cost of GP consultations and prescriptions equated to £462,827 per year per 100,000 patients. The yearly cost of prescribed medication for ARI was £319,732, at an estimated cost of £11,596,350 per year extrapolated to the UK, with 40% attributable to antibiotics. The mean cost of hospital admissions equated to a yearly cost of £981,808 per 100,000 patients. The total mean direct medical cost of ARI over 9 influenza seasons was £21,343,445 , at £136.65 (SD: £66.85) per case.Extrapolating to the UK population, for pre-pandemic influenza seasons from 2001 to 2009, the direct medical cost of ARI equated to £86 million each year. More studies are needed to assess the costs of influenza disease to help guide public health decision-making for seasonal influenza in the UK. The resource use and costs of seasonal influenza epidemics remains substantial despite many countries recommending annual vaccination for either specific population groups that are vulnerable to infection , or universal vaccination such as in the United States (US), Canada, and Australia.–4 HoweveNational influenza vaccination policies are generally guided by studies that have evaluated influenza costs or the cost-effectiveness of influenza vaccination in different settings and patient groups; in a review of 140 studies published up to 2012, the per capita cost of a case of influenza illness ranged from $30 to $64, and 22 studies reported that influenza vaccination was cost-saving. In the UThe publically-funded vaccination policy in the UK is supported by various analyses that have assessed the burden of influenza illness and costs in the UK.–12 This To help guide public health decision-making, more studies are needed that assess the burden and cost of influenza disease in the UK including episodes of influenza in primary care and secondary care, and an evaluation of risk factors associated with influenza episodes. To address this, we conducted a retrospective, cross-sectional, observational study to evaluate the primary care and directly-associated secondary care resource use, and direct medical costs of acute respiratory illness (ARI) in patients with READ codes for acute respiratory illnesses in the linked Clinical Practice Research Datalink (CPRD) and Hospital Episodes Statistics (HES) dataset during influenza seasons between 2001 and 2009. Data from the CPRD/HES dataset, the Health Protection Agency (HPA), and the Office of National Statistics (ONS), were used to identify patients with ≥1 general practitioner episode of ARI (i.e. primary care) and patients with linked secondary care data. The first analysis from the study provided data on vaccination uptake and direct medical costs by vaccination status and degree of vaccine mismatch. Here we This retrospective, cross-sectional, observational study was conducted to evaluate the resource use and direct medical costs of GP episodes of ARI and linked hospital admissions during influenza seasons in the study period of 21st January 2001 and 31st March 2009 in the UK (NCT Number: 01521416). Approval for this study was obtained from the CPRD Independent Scientific Advisory Committee (11_065) negating the need for individual patient consent. The full methods are provided in Fully anonymised data on patients who had ≥1 GP episode with a READ code identifying influenza like illnesses (ARI) were extracted from the linked Clinical Practice Research Datalink (CPRD)/Health Episode Statistics (HES) dataset for the study. Cases of ARI were identified using a broad range of READ codes describing influenza, influenza-like illness, or acute upper or lower respiratory tract infection with influenza. For each influenza peak season, ARI episodes recorded in the CPRD were identified.For patients with linked data, the HES record was assessed for hospital admissions for influenza or a complication following influenza, including data for 14 days before and after the index ARI episode. Hospitalised patients were assessed for 28 days post-discharge.Patients were categorised as low- or high-risk for influenza infection and related complications using criteria from the National Institute for Health and Care Excellence (NICE) and the UK Department of Health., 14READ codes for ARI in the CPRD and READ codes for high-risk conditions are shown in The study was conducted from 2001 to 2009 covering 9 influenza seasons, up to the outbreak of pandemic A(H1N1)pdm09 in the UK on the 27th of April 2009. GP episodes with any relevant READ code recorded during periods of influenza peak season each year were included in the study. The start and end of influenza peak season in each year was based on laboratory-confirmed reports of respiratory pathogens circulating in the UK from the Health Protection Agency (HPA) for the period November 2002 to December 2008. Peak infThe outcome measures were the incidence of: ARI GP episodes, linked hospital admissions, death, complications, and high-risk conditions: respiratory, central nervous system, diabetes, chronic heart disease, pregnant, liver disease, renal disease, and immunocompromised. The outcomes were assessed in the total population including all patients with ≥1 ARI GP episode and the hospitalized population including patients with an index ARI episode and a subsequent hospital admission. Subgroup analyses were performed by age , complication status (complicated cases and uncomplicated cases), and clinical risk group (low-risk and high-risk). Mortality was classified as being without hospital admission, in hospital, or within 28 days of discharge from hospital.GP consultations for ARI were classified as resource use in ‘primary care’. Prescriptions for medications from GPs were also classified as resource use in ‘primary care’. Medications were assessed by drug category: antipyretics/analgesics, antibiotics, amantadine, aminoglycosides, nasal decongestants, antisecretory drugs and mucosal protectants, and antihistamines. Antibiotics were assessed by class. Resource use was classified as hospitalization if it was associated with patients who were admitted to hospital or who attended a hospital out-patient appointment. Hospital resource use outcomes were: the incidence of hospital admission, mean number of unique admissions, mean length of stay per hospitalization, mean number of out-patient appointments, and route of hospital admission . Medications prescribed in hospital were not captured. The incidence of GP referrals to ambulatory out-patient appointments was also assessed.The study was based on National Health Service (NHS) records from primary and secondary care providers in the UK. The cost perspective was that of the NHS and included all primary care and hospital admissions for ARI. GP consultation costs and out-patient visit costs were from the Personal Social Services Research Unit (PSSRU) database: GP consuMicrosoft Access, Microsoft Excel and Statistical Package for the Social Sciences (SPSS).No comparisons were made between study groups so there was no target sample size. All eligible patients within the database were used in the analysis. Raw data were cleaned before analysis. It was assumed that a patient could experience only one ARI GP episode and one hospitalization on one day. Data were extracted using MySQL, and analyses were conducted in The burden of ARI, resource use, and costs were analysed descriptively in the total population and by age, complication status, and risk status. The burden and resource use data were reported as the number of patients and as a percentage of the total population. The data were also provided as the incidence of the outcome per 100,000 population in the CPRD. The data was extrapolated to the UK population using ONS; population estimates by year, and by age group are publicly available and provided end of year estimates of the resident population from 2001 to 2009: CalculatA total of 156,193 patients had ≥1 GP episode of ARI during the study period , with 82,204 patients receiving ≥1 GP prescription, at a mean of 2.5 (SD: 3.0) prescriptions per patient. The total cost of GP consultations and prescriptions during the study period was £6,506,137, equating to a yearly cost of £462,827 per 100,000 patients. The yearly cost of GP episodes of ARI ranged from £660,420 in 2007/08 to £904,644 in 2003/04. A summary of primary care resource use and costs by age group is shown in The total yearly cost of prescribed medications in the study was £319,732, and extrapolated to the UK was estimated to be £104,367,150 , with 40% of this cost attributable to antibiotics . In the A total of 1,601 (1.0%) patients were admitted to hospital, with a total of 1,856 hospital admissions. In the total population, the total cost of hospital admissions was £13,801,634, equating to a yearly cost of £981,808 per 100,000 patients. A summary of secondary care resource use and direct medical costs is shown in A total of 908 (56.7%) patients were admitted via A&E, 532 (33.2%) patients via a GP referral, and 161 (10.1%) patients via another route. The mean length of hospital stay in the total population was 11.3 (SD: 15.3) days, and the median length of hospital stay was 12.6 days. The cost of secondary care in those admitted via A&E was £9,433  per patient, and in those admitted by GP referral was £8,150  per patient. The average length of stay by year was lowest in 2002/03 (10.0 days) and highest in 2008/09 (12.9 days). The yearly cost of hospital admissions for ARI extrapolated to the UK population was £44,508,313 in 2002/03 and £85,803,090 in 2008/09 .The total mean direct medical cost in the total population was £21,343,445 , at a mean cost of £136.65 (SD: £66.85) per case . By age The highest total costs were incurred in high risk patients with CHD at £4,591,080 , and the highest cost per case was in patients with renal disease at £13,773  per case . ExtrapoThis retrospective, cross-sectional study over 9 influenza seasons between 2001 and 2009, identified 156,193 patients with ≥1 GP episode of ARI in the CPRD, of which 1,601 (1.0%) patients were subsequently admitted to hospital. The cost of GP consultations and prescriptions was £462,827 per 100,000 patients per year and the cost of hospital admissions was £981,808 per 100,000 patients per year. The total cost of prescribed medications extrapolated to the UK was estimated at £11,596,350 per year, with £4.6m (40%) attributable to antibiotics, and the direct medical cost of ARI in the UK was estimated to be about £86 million per year and £137 per case. The study shows the substantial costs of ARI in otherwise healthy people presenting to primary care, with the greatest direct medical cost component due to hospital admissions, largely among patients at high-risk of severe influenza outcomes.Tamiflu was £61,539 per year, and of Relenza was £36,003 per year.Of the 156,193 patients with an ARI GP episode, 82,204 (52.6%) patients received a mean of 2.5 prescriptions. The cost in primary care in the total population study ranged from £666,420 in 2007/08 to £904,644 in 2003/04. Antibiotics accounted for about 40% of prescribed medications, whereas antiviral use was relatively low. The most commonly prescribed antibiotic was penicillin at an average cost of £3,015,314 per year, followed by macrolides at an average cost of £1,244,624 per year, whereas the average cost of The pattern of antibiotic prescribing in our study was broadly consistent with previous reports in the UK including a CPRD study from 1991 to 1996, which showed that 59.4% of patients with influenza-related primary care episodes received medication on prescription, of which 45% were for antibiotics. In a furDespite the wide use of antibiotics, it is likely that the majority of patients who are prescribed them for respiratory illness in primary care have viral illness. For example, in a study of children aged <12 years over four winters in the UK, among about 400 cases of cough and fever for which GPs considered prescribing an antibiotic, 77% had a laboratory-confirmed viral infection. FurthermResource use among patients with a GP episode of ARI and linked HES data was substantial even though hospitalised patients represented only 1.0% of the population. A total of 1,601 patients were hospitalised during the study period, the majority of which were admitted once (87%); 10.6% were admitted twice, and two patients were admitted 5 times. The mean number of unique admissions per patient was 1.2 to 1.4 depending upon risk status. The highest rate of hospitalisation was in patients aged ≥65 years (3.7%) or <5 years (2.1%), whereas the rate of hospital admissions in the other age groups was <1%. In the previous analysis of the population stratified by influenza vaccination status, although the majority of GP episodes of ARI were in unvaccinated patients, a higher proportion of the vaccinated group (2.3%) were hospitalised than the unvaccinated group (0.5%). Hospitalised patients tended to be older with clinical risk factors associated with serious influenza outcomes, and as such, were likely to have been eligible for publically-funded vaccination.[The rates of hospitalisation observed in our study were substantially lower than those previously reported in England and Wales based on HES data, which isThe vast majority of patients received only primary care at a cost of £6,506,137 over the study period, whereas the cost of secondary care among the 1.0% of patients who were hospitalised was £13,801,634 over the study period. The mean cost of hospital admissions in the total population was £9,302 per patient, in those admitted via A&E was £9,433 per patient, and in those admitted by GP referral was £8,150 per patient. The mean cost per hospitalisation was highest in patients with heart disease , CNS disease  and renal disease . In our previous analysis, in patients aged ≥65 years, influenza vaccination coverage was high, peaking at 84.5% in 2005/06; despite this, the analysis of the total population showed that the total direct medical cost of ARI was £477.72 per patient aged ≥65 years compared with £61.21 per patient aged 19–49 years.The cost-effectiveness of seasonal influenza vaccination campaigns is difficult to measure because the clinical benefits of vaccination vary according to epidemic intensity, vaccine match with circulating strains, and risk-factors of the population; moreover, measuring absolute vaccine efficacy in elderly populations is not possible as the use of a placebo control is not ethical. To guide public health decision-making, and to assess the real world burden of influenza and the effectiveness of vaccination, many countries have established sentinel surveillance networks. Recent sentinel swabbing surveillance schemes in seasons between 2010 and 2014 in Europe and North America that assessed vaccine effectiveness for the prevention of laboratory-confirmed influenza, report adjusted effectiveness estimates from 23% to 75% in adults, with most studies showing moderate effectiveness of about 45% to 55% in the general population, and lower effectiveness in years of vaccine mismatch.–36 In a In most countries the aim of vaccinating elderly populations is to reduce hospitalisation and death, but the wide-variation in vaccine effectiveness reported in this high-risk population means that the benefit of vaccination against serious outcomes in elderly people remains a matter for debate. Estimates of vaccine effectiveness in elderly populations hospitalised with laboratory-confirmed influenza range from 33% to 86% in populations in Europe, North America, and Australia., 37–49 DUsing READ codes to identify patients with clinical influenza syndromes including a range of proxy diagnoses was the main limitation of our study. Although clinical diagnoses probably vary in their sensitivity and specificity for ARI depending upon the patient age and co-morbidities, logistic regression analysis of CPRD/HES data and weekly influenza activity from sentinel surveillance showed a strong correlation between circulating influenza viruses and clinical episodes in the study . However,In summary, this retrospective, cross-sectional study using the CPRD and linked HES databases in the UK showed that the cost of ARI in primary care was £462,827 per 100,000 population per year and the cost of linked hospital admissions was £981,808 per 100,000 population per year. Extrapolating to the UK population, for 9 influenza seasons from 2001 to 2009, the direct medical cost of ARI was estimated to be £137 per case, equating to £86 million per year.S1 Data(DOCX)Click here for additional data file.S2 Data(DOCX)Click here for additional data file.


The aim of this study was to analyze the effects of an 8-week whole-body vibration (WBV) on the quality of life, physical fitness, body composition, glycosylate hemoglobin (HbA1c), lipid profile, and foot health status in people with type II diabetes mellitus (T2DM). It was performed as a double-blinded randomized controlled trial of 90 people with T2DM. Primary care facilities were used. The 8-week WBV training consisted of maintaining a knee flexion at 45° during five to nine series of 30–60 s in a vibration frequency that oscillated between 12.5–18.5 and 30 s of recovery between series. The placebo group had to perform the same protocol but without vibration. Participants performed the protocol three times per week. The WBV training significantly reduced the fat mass (%) of people with T2DM. However, significant effects of WBV training were not found in the quality of life, physical fitness, foot health status, lipid profile, blood pressure, fasting blood glucose, or HbA1c. Nevertheless, within groups enhances were found in HbA1c, blood pressure, fasting blood glucose, foot health status, health-related quality of life, timed-up and go test, and chair-stand test in both WBV and placebo groups. WBV was shown to be beneficial for reducing the fat mass and lipid profile of people with T2DM. The improvements of the placebo group could be due to both the social benefits of enrolling in an intervention and the physical fitness benefits of isometric contractions. Further studies are needed to clarify the effects of WBV and to establish a dose–response relationship in people with T2DM. Diabetes Mellitus (DM) is defined as a state of hyperglycemia, in either fasting or postprandial states 1). DM is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both . DM is a. Type 2 Physical exercise has become a therapy for people with T2DM , improviExercises based on whole-body vibration (WBV) training have shown to enhance balance, mobility muscle strength, pain, cardiorespiratory fitness, and bone density, in both healthy and clinical populations ,21,22,23In addition, Gomes-Neto, de Sa-Caputo, Paineiras-Domingos, Brandao, Neves, Marin, Sanudo and Bernardo-Filho  stated tHowever, Gomes-Neto, de Sa-Caputo, Paineiras-Domingos, Brandao, Neves, Marin, Sanudo and Bernardo-Filho  stated tThis study was conceived as a double-blinded, randomized controlled trial where participants were randomly allocated into two groups: whole-body vibration (WBV) and placebo group (PG). All the procedures were approved by the University research ethics committee . The trial was prospectively registered at the International Standard Randomized Controlled Trial Number Registry (ISRCTN16866781).The intervention was carried out in the Primary Care Center “Manuel Encinas” from the city of Caceres, in Extremadura, Spain from March 2013 to June 2013.The HbA1c was used to estimate the sample size. Accepting an alpha risk of 0.05 and a beta risk of 0.05 in a bilateral contrast, at least 40 participants in the WBV group and 40 in the PG are required to detect a difference equal or greater than 0.57 units . Taking (a)Men or women with T2DM diagnosed between 40 and 85 years old. T2DM is characterized by hyperglycemia caused by insulin resistance .(b)Have read, accepted and signed the written informed consent.Finally, 90 T2DM patients were included in this randomized controlled trial. All of them were recruited until 31 January, 2013. Participants inclusion criteria were:(a)have Type I diabetes mellitus diagnose, since the aetiology completely differs from T2DM.(b)have a condition that may make the high intensity exercises contraindicated, such as retinopathy, musculoskeletal injuries, major balance problems or high risk of thrombosis.(c)Be under psychotropic or neurotoxic treatment.(d)Be exposed to neurotoxins .(e)Receive radiation therapy.(f)High risk of non-diabetic neuropathy .(g)Have or had a job with high exposure to mechanical whole-body vibrations.(h)Have performed whole-body vibration exercises prior to this intervention.Moreover, participants were excluded if they:Participants were randomly allocated into the two groups (WBV or PG) by a technician using random numbers. Participants allocated to WBV and PG were classified as A and B respectively. This researcher did not take part in the acquisition, intervention or data analysis. A technician who was blinded to the grouping allocation developed the intervention and had to apply protocol A or B for each participant. The placebo group was led to believe that they were receiving a WBV below the vibration threshold that it was able to detect. For this purpose, the Galileo Fitness platform was connected through wiring to a screen where the participant had the values of vibration duration and frequency amplitude, but it really was a software that controlled two speakers placed inside the vibration platform.The procedures conducted by WBV and PG during the 8-weeks training are described below. Whole-body vibration group protocol: Placebo group protocol: As commented above, participants of PG believed that they were receiving a WBV below the vibration threshold (unable to detect). For this purpose, the Galileo Fitness platform was connected through wiring to a screen where the participant had the values of vibration duration and frequency amplitude, but it really was a software that controlled two speakers placed inside the vibration platform. Previous studies have performed a similar procedure ,34.All participants, irrespectively of their group allocation, were required to: (1) stand on the platform on their feet at an equal and standardized distance from the middle axis (4 mm of vibration amplitude); (2) keep their eyes fixed forward with the back straight; (3) maintain a knee flexion at 45°; and (4) get on the platform without shoes. In order to ensure the security of the protocol, all participants were encouraged to follow the instructions. Moreover, a physical therapist supervised the intervention in order to correct the posture when appropriate and to control the whole-body vibration protocol for each training day. Additionally, the intervention protocol was progressive in both vibration time and intensity as shown in Lipid profile, HbA1c, fasting blood glucose, body composition, and blood pressure: The lipid profile  and the HbA1c were obtained through a blood sample in the morning after an overnight fast. Moreover, participants were measured and weighed using the Tanita Body Composition Analyzer BC-418 MA. The blood pressure was measured using an aneroid sphygmomanometer.Foot health status: The Foot Health Status Questionnaire (FHSQ) was used in the present study. It is composed of three sections. The first section includes 13 questions and evaluates four dimensions . The second section includes 20 questions and evaluates the four dimensions left . Each question is valued following a Likert-type scale and the scoring goes from 0–100, where 0 is the worst foot health status and 100 is the best possible foot health status. Lastly, the third section refers to the socio-demographic values of the sample. The validated version adapted to Spanish was employed .Health-related quality of life: The 15-D Health Questionnaire  was usedChair-stand test: This test evaluated lower-limb strength by counting the number of times the participant is able to stand up from a sitting position  and then sit down as many times as possible in 30 s . This teTimed-up go (TUG): The TUG (3m) was performed two times, with a 5-min rest in between. The first repetition was for familiarisation and the second was the test measure. All participants performed a light warm-up which included walking and joint mobility for 5 min. Reliability analysis for this test in the DM population has been previously published ,39.The SPSS statistical package  was used to analyse the data. Non-parametric tests were conducted based on the results of Shapiro-Wilk and Kolmogorov-Smirnov tests.Data from all 90 initial participants were used to conduct the intention-to-treat analysis by multiple imputation (MI) of missing values following the Sterne, et al.  guidelinMann-Whitney U test was employed to study the differences at baseline in the physical function, self-perceived health foot status, HbA1c, fasting blood glucose or body composition variables among others. Moreover, the difference between post and pre was calculated for each variable. These differences were used to study between-group effects of the intervention by the Mann-Whitney U test in the different variables.Moreover, Wilcoxon signed-rank test was used to explore the within groups effects for each variable (WBV and placebo group separately). Additionally, effect sizes were calculated for the non-parametric tests through r, which is classified as follows: 0.5 is a large effect, 0.3 is a medium effect, and 0.1 is a small effect ,42.n = 45) and PG (n = 45). Six and eight participants of the WBV and the PG respectively did not attend the final evaluation. In this regard, intent to treat analysis were applied to this data.The flow diagram of the participants is depicted in The main characteristics of the included participants are shown in p-value = 0.006), total body water , HDL  and a significant decrease in BMI , fat mass , total cholesterol , systolic blood pressure , fasting blood glucose  and HbA1c . The PG showed significant decreases of weight , BMI , systolic blood pressure , fasting blood glucose , and HbA1c . Between-group comparisons showed that WBV significantly reduced the fat mass .p-value = 0.015) and vigour FHSQ item  respectively. Mann-Whitney U did not show any significant effect.Our study showed that 8 weeks of WBV training had a significant effect on the body composition, reducing the fat mass of people with T2DM. However, significant effects on mobility, HbA1c, blood glucose, blood pressure, lipid profile, or health-related quality of life were not found. Nevertheless, within-groups improvements in WBV in physical fitness, body composition, foot health status, systolic blood pressure, HbA1c, lipid profile or fasting blood glucose showed that WBV training could be included as part of therapeutic intervention for people with T2DM. Importantly, side effects were not reported for any of the participants at 12.5–18.5 Hz.In line with our result, previous studies have shown significant effects of WBV on the body composition of older adults with T2DM. In this regard, Sanudo, Alfonso-Rosa, Del Pozo-Cruz, Del Pozo-Cruz, Galiano, and Figueroa  found a The effects of WBV training on quality of life and foot health in people with T2DM have been poorly studied. Regarding quality of life, previous studies showed that WBV could improve the quality of life in older populations  and otheResults of physical function indicated that both groups (WBV and PG) obtained within-group improvements in the chair stand test and TUG. However, significant effects of the WBV training were not found. Nevertheless, previous studies have reported positive effects of WBV (with or without complementary exercises) on the physical function of people with T2DM . MoreoveIn most of the studied variables, an improvement could be observed in both the EG and placebo group after 8 weeks of intervention. It could hypothetically be explained by two reasons. First, people with T2DM have high levels of physical inactivity . Simply N = 90) did not allow to create different group of patients with different diabetic conditions . Consequently, the subgroups would have had a sample size too small to make comparisons with enough statistical power strength. In the same line, we would have also found the same problem in a study that aimed to compare the effects of different vibration frequency protocols. Therefore, future studies should investigate both the effects of WBV training in different diabetic conditions and the dose-response of different WBV protocols. Lastly, this randomized controlled trial included a placebo group that did not statistically differ in any of the variables at baseline when compared with the WBV group. This group followed the same protocol to WBV but with an infra-threshold vibration (simulated with two speakers placed under the vibration platform). Therefore, they only had to perform the same protocol isometric contraction on the platform. Taking into account the physical inactivity level of people with T2DM [The current study has some limitations that should be taken into account. Firstly, the relatively small sample size (ith T2DM , this coWBV reduced the fat mass of people with T2DM. However, significant effects were not found in HbA1c, physical function, foot health, and quality of life. Further studies are needed to clarify the effects of WBV in people with T2DM.


Postural tachycardia syndrome (POTS), characterized by chronic (≥6 months) orthostatic intolerance symptoms with a sustained and excessive heart rate increase while standing without postural hypotension, is common in children and adolescents. Despite the unclear pathogenesis of POTS, the present opinion is that POTS is a heterogeneous and multifactorial disorder that includes altered central blood volume, abnormal autonomic reflexes, “hyperadrenergic” status, damaged skeletal muscle pump activity, abnormal local vascular tension and vasoactive factor release, mast cell activation, iron insufficiency, and autoimmune dysfunction. A number of pediatric POTS patients are affected by more than one of these pathophysiological mechanisms. Therefore, individualized treatment strategies are initiated in the management of POTS, including basal non-pharmacological approaches  and special pharmacological therapies . As such, the recent progress in the pathogenesis, management strategies, and therapeutic response predictors of pediatric POTS are reviewed here. Postural tachycardia syndrome (POTS) is one of the common forms of chronic (at least 6 months) orthostatic intolerance (OI), and most of the cases have presyncope symptoms accompanied by inappropriate sinus tachycardia with normal blood pressure in an upright position , 2. The Because of the multisystem discomforts of pediatric POTS patients, there are significant deleterious effects on individual quality of life –8. In peTo date, although the precise pathophysiology underlying pediatric POTS remains unclear, there have been some significant reports indicating that POTS might be multifactorial and varied in different subpopulations of young POTS patients , 6, 12. Under physiological conditions, the blood flow is redistributed when an individual changes position from lying down to standing. Blood volume shifts from the upper part of the body to the lower part and the splanchnic circulation, as well as from the vascular system into the interstitial space owing to gravity while in the upright position . StandinTo compensate for the changes in orthostatism, the body has a series of regulations to restore venous return and cardiac output , 15. ImpThe pathophysiology of POTS is complicated and obscure , 12. CurDecreased red blood cell volume or low blood volume has been found in many pediatric POTS patients , 20, 21.Stewart and Montgomery  reportedIn light of the important role of the RAAS in regulating human neurohormones of plasma volume, a perturbed RAAS axis, which is disabled to facilitate the enlargement of blood volume in response to the hypovolemia of POTS patients, might be one of the pathophysiological changes in POTS . SeveralCompared to healthy people, patients with POTS demonstrate excessive blood volume accumulation in the lower extremities and visceral circulation, which results in an obvious decrease in blood volume in venous return to the heart and subsequent cardiac ejection during orthostatic stress . The aboSLC6A2) gene impair the removal of norepinephrine in the synaptic cleft and reduce NET-dependent norepinephrine reabsorption  and constitutively expressed in the endothelium, is known as a vasorelaxant factor and plays a crucial role in regulating the function of vascular endothelial cells (2S), a gasotransmitter alongside NO, exerts a low concentration-produced contraction or high concentration-dependent relaxation of blood vessels (2S has been detected to be obviously higher in pediatric POTS patients than that in control group (2), another gaseous molecule, has recently been found to have vasorelaxant effects (2 levels were significantly higher in children with POTS than in healthy controls and were positively related to the maximum HR of all the study participants (in vitro experiment showed that resistin could decrease endothelial NOS expression in human coronary artery endothelial cells (in vivo (To further explore the mechanism for vascular tension dysfunction, some studies have been designed, and the results show that bioactive gaseous regulatory molecules and vasoactive peptides are involved in the development of abnormal partial vascular tension and impaired endothelial cell function in children and adolescents with POTS , 59–63. al cells  reportedal cells . Hydroge vessels . Erythrool group , 63. Sul effects , 65. Furicipants . The thricipants , 60. Addicipants , has beeicipants . C-type icipants . The poticipants . Uprighticipants . The resicipants , has beeicipants . An in val cells . The seral cells . These f(in vivo . Taken t(in vivo , 54.As the richest transition metal ion in humans, iron can cause a decrease in vasodilation by inhibiting the biosynthesis, transportation, transformation, and signal transduction of NO , 77. LowIn an evaluation of young females with POTS, Shibao et al.  found thAutoimmune disturbance has been considered as one of the mechanisms involved in POTS due to frequent findings of autoantibodies in patients , 86, 87.Full recovery is possible for POTS in children and adolescents, but it is difficult to treat patients because of inconsistent and poor therapeutic efficacies . Thus, cHealth education on POTS is needed for young patients and their guardians who should understand the potential precipitating factors and avoid them –8, 96. OIn addition, appropriate physical exercise to enhance muscle pump function of limbs and autonomic nervous system exercises to improve autonomic tone are also recommended for children with POTS , 98. The2 (Children and adolescents with POTS, especially those with 24-h urinary sodium excretion <124 mmol  or a BMI2 , are enc2 . However2 , 95.2 (Non-pharmacological interventions should be attempted first in all pediatric POTS patients. If these interventions are ineffective, pharmacological therapies should be applied to solve the specific problems , 95, 96.2 , have be2 . When bo2 . Fludroc2 . In addi2 , suggestFor children with severe symptoms or a risk of injury with unobvious presyncope that remarkably affect the quality of life and for those who do not demonstrate a good response to health training and salt supplementation therapy, special vasoregulation-related pharmacological interventions should be considered , 96.2S production in erythrocytes >27.1 nmol/min × 108 cell, with a sensitivity of 78.9% and a specificity of 77.8% (Midodrine hydrochloride, a drug that is enzymatically hydrolyzed as a selective α1-adrenoceptor agonist desglymidodrine by oral administration , constriof 77.8% ; midregiof 77.8% ; copeptiof 77.8% ; and SBPof 77.8% . Additioof 77.8% . Midodriof 77.8% . Since mof 77.8% , 98, 106Adrenoceptor blockers can be divided into non-selective blockers for β1 and β2 receptors and β1-selective blockers, which have higher selective affinity for β1 receptors than for β2 receptors . The latAlthough evidence hints that MCA and autoimmune disorders take part in the pathogenesis of POTS , 86, 88,Although great efforts have been made in exploring the pathogenesis of pediatric POTS, the precise mechanisms for POTS have not yet been totally elucidated , 6, 96. GC: literature review, interpretation of data, and first draft of the manuscript. JD: design, organization, and editing of the manuscript. HJ: critical review and editing of studies cited in the manuscript. YH: concept and design of the manuscript, critical review, and editing of the manuscript. All authors: contributed to manuscript revision, read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Increasing studies indicate that acupuncture can be used for treating vestibular migraine (VM), but current evidence remains inconclusive. Thus, this protocol aims to evaluate the evidence regarding the efficacy and safety of acupuncture for VM prophylaxis by conducting a systematic review and meta-analysis.Studies will be retrieved by searching electronic databases from their inception to December 2020, including EMBASE, PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), and Chinese Science and Technology Periodical Database (VIP). Eligible randomized controlled trials involving acupuncture for VM prophylaxis will be included. Study screening, data collection, and assessment for risk of bias will be executed by 2 independent reviewers. Meta-analyses will be conducted, followed by subgroup analysis if significant heterogeneity is detected. Sensitivity analysis and summary of the strength of the evidence will also be performed.The results of the present systematic review and meta-analysis will verify the efficacy and safety of acupuncture for VM prophylaxis.This review will determine the efficacy and safety of acupuncture on VM prophylaxis. The findings are expected to verified whether acupuncture can be an alternative treatment for VM prophylaxis.Given that a systematic review and meta-analysis will not involve private information of individuals, ethical approval is not required. Relevant results and findings will be submitted to an academic journal for peer reviews.CRD42020202588. Its major symptoms of vertigo and migraine can coexist in 3 ways, in which vertigo can attack before, or after, or coincident with migraine. VM can occur at any age, but the most common age category is between 30 and 40 years. For gender differences, VM occurs about 1.5 to 5 times more often in females than in males.,4 Epidemiological surveys revealed that its 1-year prevalence is 2.7% among adults in the USA. The lifetime prevalence of VM is about 1% and a 1-year prevalence of VM is about 0.9% in general population. Moreover, it accounts for about 9% of patients in migraine clinics, 11% of patients in dizziness clinics, and 4.2% to 29.3% of patients in otolaryngology clinics.,9 Nevertheless, the accurate diagnostic of VM is low. A recent study found that the referring doctors had suspected only 1.8% of the young patients to have VM in a tertiary vertigo center, whereas a diagnosis was made in 20.2%. Common comorbidities of VM include Meniere disease and emotional disorders, especially anxiety and depression, which have brought a huge global burden of disease.–13 Nevertheless, the pathogenesis of VM remains poorly understood and needs further investigation.Vestibular migraine (VM) is one of the most common causes for vestibular diseases, which ranks the second place following benign paroxysmal positional vertigo (BPPV). Frequent VM attack can seriously affect patients’ daily life and work, thus, prophylaxis of VM is of great significance for patients. There is a consensus among experts that prophylaxis treatment is vital for VM patients if the frequency of vertigo/migraine attacks is at least 3 times per month in the last 3 months, or patients have poor response to treatment in the acute phase of VM.At present, the treatment of VM mainly targets at acute stage and prophylaxis. Pharmacological treatments for acute VM mainly choose triptans and pharmacological treatments for VM prophylaxis include western medication for preventing migraine, such as metoprolol, propranolol, valproic acid, topiramate, and amitriptyline. However, pharmacological treatments are often associated with various side effects, such as dizziness, paraesthesia, dyspepsia, nausea, dry mouth, chest discomfort, and somnolence.,17 which are major symptoms of VM. Meanwhile, it can also improve emotional disorders, which are common comorbidities in VM. Thus, acupuncture might be a favorable therapy for treating VM. In recent years, there are increasing clinical trials investigating the efficacy and safety of acupuncture for VM prophylaxis, but current evidence is inconclusive. Therefore, this will be a protocol for the first systematic review and meta-analysis that aims to ascertain the evidence for efficacy and safety of acupuncture on VM prophylaxis.As an important component of complementary and alternative medicine, acupuncture can promote recovery of health by inserting needles and stimulating specific points on the body. Given to its role as an effective and safe nonpharmaceutical therapy for treating a wide range of diseases, acupuncture is gaining acceptance all over the world. Acupuncture is widely used in treating migraine and vertigo/dizziness,22.1 to report the findings.This protocol for a systematic review and meta-analysis is conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols (PRISMA-P)This PRISMA-based systematic review and meta-analysis has been registered in PROSPERO with the registration number CRD42020202588.2.22.2.1We will include studies of randomized controlled trials (RCTs) involving acupuncture for VM prophylaxis. Studies in nonrandomized or uncontrolled designs will be excluded. Language restrictions will not be imposed.2.2.2Participants with a confirmed diagnosis of VM based on internationally recognized diagnostic criteria  will be included. Meanwhile, patients need prophylaxis treatment when vertigo/migraine attacks at least 3 times per month in the last 3 months, or vertigo/migraine days are at least 4 days per month, or patients have poor response to treatment in the acute phase of VM. All patients with age ≥18 years, male or female.Participants of the following conditions will be excluded: Patients do not meet the diagnostic criteria and age criteria; and vertigo and headache are caused by other diseases, such as BBPV.2.2.32.2.3.1The modalities of experimental interventions include acupuncture therapy alone, and acupuncture combined with another widely recognized active therapy . Acupuncture therapy is defined as any acupuncture modality, such as manual acupuncture, electroacupuncture, auricular acupuncture, scalp acupuncture, warming-needle moxibustion, and so on.2.2.3.2The modalities of control interventions include widely recognized active therapies for prophylaxis of VM, such as preventive drugs; no treatment or waiting list; and placebo controls: such as sham acupuncture, placebo drugs, sham interventions.2.2.42.2.4.1Primary outcomes consist of vertigo/migraine episodes: including vertigo/migraine days and vertigo/migraine frequency per month; intensity of vertigo/migraine measured by acknowledged scales, such as visual analogue scale (VAS); and response rate.2.2.4.2Secondary outcome measures include vertigo-related assessment scale, such as the Dizziness Handicap Inventory (DHI) scale; anxiety level assessed by valid questionnaires, such as the Generalized Anxiety Disorder-7 (GAD-7) scale and the Hamilton Anxiety Scale (HAMA); depression level measured by valid questionnaires, such as the Patient Health Questionnaire (PHQ-9) scale and the Hamilton Depression Scale (HAMD);patients’ quality of life measured by acknowledged scales, such as the 36-Item Short Form Health Survey (SF-36); and adverse events.2.3Studies will be retrieved by searching the following electronic databases from their inception to December 2020, which include PubMed, Web of Science, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), and Chinese Science and Technology Periodical Database (VIP). We will also scan references of all eligible literature to identify additional publications. The search strategies are based on a combination of subject headings  and the following search terms: acupuncture, needling, manual acupuncture, electroacupuncture, auricular acupuncture, warming-needle moxibustion, vestibular migraine, migraine-associated dizziness, migraine-associated vertigo, vertiginous migraine, hemicrania, cephalalgia, cephalagra, migraine and randomized controlled. Corresponding terms in Chinese will be searched in Chinese databases. The example of search strategy for PubMed is displayed in Table 2.42.4.1Two independent reviewers (TYH and JH) will screen papers to include eligible RCTs by reading titles, abstracts of studies according to the inclusion/exclusion criteria. The full text of potentially qualified studies will be reviewed to confirm eligibility. The study screening process in a flow chart is displayed in Figure 2.4.2 If there is controversy during assessment for risk of bias, it will be arbitrated by a third reviewer (JH).Two reviewers (TYH and FFS) will perform the assessment of risk of bias independently based on the Cochrane risk-of-bias tool. In details, risk of bias of a included study will be graded into 3 categories as either: “unclear,” “low,” or “high” risk for 7 domains as follows: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete data, selective outcome reporting, and other bias.2.4.3Effect sizes will be measured by using the risk ratio and 95% confidence interval (95% CI). Odds ratio (OR) or relative risk (RR) will be analyzed for dichotomous outcomes data, while the weighted mean difference (WMD) or the standard mean difference (SMD) will be analyzed for continuous outcomes.2.4.4If relevant data are missing in certain studies, we will manage to obtain missing data by contacting the authors of the corresponding studies via email. If the authors do not reply to our request, an intention-to-treat analysis will be employed in the absence of missing data.2.4.5I2 values, which are graded into 4 categories based on the Cochrane Handbook: little or no heterogeneity (I2: 0–40%); moderate heterogeneity (I2: 30–60%); substantial heterogeneity (I2: 50–90%); and considerable heterogeneity (I2: 75–100%).Heterogeneity assessment will be quantified based on the Chi-squared test and 2.4.6If there are sufficient studies included in meta analyses, reporting biases will be determined via funnel plots.2.4.7I2 ≥50%).Data synthesis and analysis will be conducted by using Review Manager 5.3 . Fixed effect model will be employed if little or no heterogeneity is detected; while random effect model will be used if considerable heterogeneity is detected ; types of control interventions; measurement time points of primary outcomes; and age groups of patients.2.4.10 will be used to assess the strength of evidence for all meta-analysis outcomes, which is graded into 4 levels: high, moderate, low, and very low quality.The Grading of Recommendations Assessment, Development and Evaluation (GRADE)3 and has a significantly negative impact on patients’ daily life and work. Meanwhile, it will impair their psychology and/or emotional states. However, the pathophysiology of VM is poorly understood, and the majority of available hypotheses are based on the pathogenesis of migraine.VM is a recurrent vestibular disease that gains increasing attention by researchers and clinicians in recent years. It is characterized by vestibular symptoms and migrainous symptoms As a major part in complementary and alternative medicine, acupuncture is frequently used for treating migraine, vertigo, and emotional disorders for a long history, which are primary symptoms and comorbidity of VM. In past few years, increasing clinical trials indicated that acupuncture can be used for treating migraine, vertigo, and emotional disorders synchronously, so it is likely to be an effective therapy for VM. There are also some published studies of RCTs in favor of acupuncture for treating VM.,27 In addition, acupuncture has other advantages of simple operations, low medical cost, and less side effects. Nevertheless, to date, this is a lack of available evidence for the efficacy and safety of acupuncture for prophylaxis treatment of VM.As conventional treatment, western medicine often just targets at single symptom of VM. Moreover, it is often limited by poor patient adherence because of its unavoidable side effects, such as nausea, dry mouth, and dizziness.This present study will be the first systematic review and meta-analysis that aims to investigate the evidence of acupuncture for VM prophylaxis. It will verify whether acupuncture for VM prophylaxis is safe and effective. The findings of this study are expected to provide an alternative treatment option for VM patients and provide additional guideline in VM treatment for both clinicians and policy makers.Nevertheless, the present study also has several limitations to be addressed. First, VM diagnostic criteria are relatively subjective, and there are no objective measurement indicators, which will have an impact on the inclusion criteria of patients. Second, given that the literature retrieved in this study will be restricted to English and Chinese mainstream databases, publication bias might exist. Third, at present, there may not be many eligible trials involving acupuncture for prophylaxis treatment of VM to be included in the meta-analysis.TYH and JH designed the trial protocol. TYH and AJZ drafted the manuscript. BJ and FFS planned a data analysis solution. All the authors have read, revised, and approved this version of the manuscript.Investigation: Fengfei Shen.Writing – original draft: Tianye Hu, Jin Hu.Writing – review & editing: Aijun Zhang, Bin Jiang.The funding details have been updated to add “the Project of Zhejiang Administration of Traditional Chinese Medicine (grant no.2021ZQ084)”.


Prison inmates are highly susceptible for several infectious diseases, including vaccine-preventable diseases. We conducted a systematic international literature review on vaccination coverage against hepatitis B virus (HBV), hepatitis A virus (HAV), combined HAV/HBV, tetanus-diphtheria, influenza, pneumococcal, and combined measles, mumps, and rubella (MMR) in prison inmates, according to the PRISMA guidelines. The electronic databases were used Web of Science, MEDLINE, Scopus, and Cinhal. No language or time limit were applied to the search. We defined vaccination coverage as the proportion of vaccinated prisoners. There were no limitations in the search strategy regarding time period or language. Of 1079 identified studies, 28 studies were included in the review. In total, 21 reported on HBV vaccine coverage (range between 16–82%); three on HAV (range between 91–96%); two studies on combined HAV/HBV (77% in the second dose and 58% in the third); three studies on influenza vaccine (range between 36–46%), one of pneumococcal vaccine coverage (12%), and one on MMR coverage (74%). We found that data on vaccination coverage in prison inmates are scarce, heterogeneous, and do not include all relevant vaccines for this group. Current published literature indicate that prison inmates are under-immunized, particularly against HBV, influenza, MMR, and pneumococci. Strengthen immunization programs specifically for this population at risk and improvement of data record systems may contribute to better health care in prisoners. Today, there are more than 11 million prison inmates around the world . This inMany prevalent communicable diseases in prisons can be prevented by vaccination. Even though several of these vaccines should be administered as a part of routine national immunization programs during early childhood, factors such as social marginalization, migration, and coming from areas with poor access to health care may contribute to a lower immunization rates, with a higher number of individuals susceptible to vaccine-preventable diseases in prisons around the world .The higher prevalence of communicable diseases among prison inmates may contribute as well to the risk of infectious diseases in the general population since prisoners are often released after short periods of incarceration back into society ,6,7. On Several international health authorities and organizations including the World Health Organization , the EurHowever, local implementation of these recommendations largely varies across countries; while high-income countries might have specific vaccination guidelines for this group ,16,17,18Estimates of vaccine coverage are one of the main tools that can be used to indirectly estimate the level of immunity against diseases in any given population. Vaccine coverage estimates also reflect the level of adherence to recommendations for immunization and allow us to tailor preventive interventions according to the specific immunization gaps in the population. In this systematic review, we aimed to identify studies on vaccination coverage against several vaccine-preventable diseases in prison inmates and thus identify areas for possible public health interventions. A systematic review of the international literature was carried out following the PRISMA methodology to compile the existing evidence on vaccination coverage in prisons at international level.The literature search by two reviewers was performed on 20 February 2020 in the electronic databases Web of Science, MEDLINE, Scopus, and Cinhal. The search keywords that were used were: vaccines, vaccination coverage, immunization programs, prisons, prisoners, and inmates in jail. In the search string, the operators “OR” and “AND” were used when relevant, obtaining the following search string: ((((((((“Vaccines”[Mesh]) OR “Vaccines”[Title/Abstract])) OR ((vaccination Coverage[MeSH Terms]) OR vaccination Coverage[Title/Abstract])) OR ((Immunization Programs[MeSH Terms]) OR Immunization Programs[Title/Abstract]))) AND ((((((“Prisons”[Title/Abstract]) OR Prisons[MeSH Terms])) OR ((prisoners[MeSH Terms]) OR prisoners[Title/Abstract])) OR “inmate”[Title/Abstract]) OR “jail”[Title/Abstract])) AND Humans[Mesh]). No language or time limit were applied to the search.The following steps were carried out in the bibliographic search: analysis of the documents with extraction of the most relevant information; synthesis of the information that was ordered, combined and evaluated in a comparative way; finally, the end of the search, where we obtained the selected articles included in the review .The articles were selected through the screening of titles, abstracts and by reading the full text articles, based on predefined inclusion and exclusion criteria based on the PICO  model. Prisoners were defined as any person admitted to prisons. Correctional facilities were defined as jails or prisons and custodial settings that function as prisons, excluding immigrant centers and police detection rooms. The intervention included any strategy that provided data on HIV status and vaccination against communicable diseases upon entry and during prison stay (including outbreak situations). The researchers considered studies with data from community settings, those comparing the inmate population and community settings, those that compared inmates with each other, and those that compared between different risk groups. The following items were considered: people reached by a certain intervention, people who have completed the vaccination, people with serological status, and vaccination coverage. Vaccination coverage was defined as the proportion of prisoners who receive the vaccines recommended by the prison health authorities of their country.The selected articles had to provide the vaccination coverage of the prisoners regardless of the vaccine studied. Systematic reviews, articles that did not study vaccines, those that did not provide data on vaccination coverage, and those carried out outside the prison setting were excluded. All search and selection steps were performed was made by three independent researchers  and the results were compared and discussed between the three. All selected registries (including articles that raised doubts) were verified by an investigator with experience in the field of vaccine research (JT). The outline of the review can be seen in Data from selected studies were extracted into tables designed by one investigator and reviewed by a second investigator. The tables contained information on the characteristics of the study: author, year of publication, country (ISO 3166-2), type of study, vaccine studied, methodology for obtaining results , type of vaccination carried out , vaccination regimen used during the study, study sample, and vaccination coverage.Of a total of 1079 results obtained in the four databases consulted, 475 articles were excluded because of duplicates. Subsequently, the remaining 604 articles were reviewed, 576 of which were excluded when applying the inclusion and exclusion criteria, resulting in a final sample of 28 articles .n = 9) [n = 5) [n = 5) [n = 3) [The United Kingdom is the country from which most studies on vaccination coverage in prisoners were retrieved (n = 9) ,41,44,45 [n = 5) ,38,39,40 [n = 5) ,31,42,46 [n = 3) ,26,32. T [n = 3) , Italy [ [n = 3) , Luxembo [n = 3) , Canada  [n = 3) , and Den [n = 3) .We found the following vaccines and vaccine-preventable diseases studied: hepatitis B virus (HBV), hepatitis A virus (HAV), combined HAV/HBV, influenza, pneumococcal, and combined measles, mumps, and rubella (MMR) vaccines. n = 10) [n = 5) [n = 3) [n = 5) [n = 5) [The methods used to investigate the vaccination status of the inmates were: serological testing (n = 10) ,44,45,46 [n = 5) ,37,38,40 [n = 3) ,31,36, t [n = 5) ,30,32,34 [n = 5) ,39,41,43n = 21) [n = 7) [n = 6) [n = 21) [n = 3) [n = 3) [n = 2) [n = 1) [n = 1) [The aim of the studies was to evaluate systematic vaccination or relevant update of the adult vaccination program n =  [21,22,2n = 21) ,39,40,41 [n = 7) ,43,44,45 [n = 6) ,37,43,46 [n = 6) ,43,44,45 [n = 6)  and in a [n = 6) . In 11 s [n = 6) , in 4 st [n = 6) ,28,38, i [n = 6) ,40. The  [n = 3) ,29,39, H [n = 3) ,36,37, c [n = 2) ,38, pneuAmong the 21 studies that focused on HBV vaccine, five studies detailed the reasons why prisoners were not vaccinated ,23,24,25The three studies that provided data on HAV vaccination coverage in prisons are European ,36,37. O®, in men who have sex with men. The coverage achieved was 77% for the second dose, 58% for the third and 11% for the fourth. In the same study, they offered HBV vaccination with the traditional schedule (at 0–1 month and 4–6 months) to all prisoners, with a coverage of 59% for the second dose and 22% for the third dose. The study from Nijhawan et al. [Two of the studies in our systematic reviewed explored the HAV/HBV combination vaccine ,38. The Gilles and colleagues  assessedThere is only one study reporting on mumps in prisoners in the context of an outbreak in Canada in 2011, in which the MMR vaccine was offered to the entire inmate population. They campaign achieved 83% of vaccination coverage in prisoners and 36% in staff .Vaccination coverage in prison inmates has been a subject of limited interest. Most studies deal with HBV and its direct relationship with a risk group (IDUs or HCV positive inmates) ,43,44. IEight studies from the United Kingdom on HBV vaccination coverage have been published, and despite policy changes favoring vaccination in prisons in the 1990s, no major advances have been observed in vaccine coverage . In 2001Regarding the type of interventions, accelerated HBV vaccination programs improved compliance and may contribute to achieve higher immunization rates, particularly for the high proportion of inmates serving short sentences ,23,32,35The main reasons associated with non-vaccination when carrying out an intervention program in prisons were the release before the administration of the vaccine, previous or current infection, having previously received the vaccine, and refusal to vaccination ,24,25,33In this review, a limited number of studies on vaccination coverage of HVA, influenza, pneumococcal, and MMR in prisoners were identified and none on diphtheria-tetanus or BCG were included, similarly to what was published in the review by Madeddu et al.  in 2019,Even though HAV vaccination of inmates is not routinely recommended by the CDC, vaccination of certain risk groups including, among others, individuals with underling chronic liver diseases, HBV, HCV, and HIV infected individuals, pregnancy, men who have sex with men, and homeless people, all conditions that may be present among inmates ,37. HAV Few published studies on combined HAV/HBV vaccination were conducted in the US. In a recent review by Madeddu et al.  in 2019,Regarding influenza, current guidelines recommend offering seasonal influenza vaccine to high-risk groups in the general population, including the elderly and chronically ill, and do not refer to incarcerated persons specifically ; except The only published study on MMR vaccine coverage summarizes the general conclusions of the other studies included in the review: data on vaccine coverage in prisoners are scarce, state vaccination registries are not usually available to verify the vaccination status of prisoners, and inmates are an accessible risk-group . To thisThe most common vaccination modality in a prison is the systematic approach, either as a primary vaccination, as booster or as a post-exposure dose, although massive vaccination programs are also used to control outbreaks. We must remember that, similarly to the general population, acceptance of vaccination is voluntary.Despite international guidelines and the publication of many evidence-based interventions that demonstrate benefit, a huge gap remains in the introduction and expansion of vaccination programs in prisons in both low- and high-income countries. Cooperation and coordination between the penitentiary and public health systems is necessary to guarantee equity in access to prevention services for the population during incarceration .The extreme sociodemographic heterogeneity of the prisoners, influenced by migration, makes it difficult to assume that the vaccination coverage of this specific population resembles to what otherwise found in the general population at any given time. Carrying out an intervention in closed populations with a large proportion of susceptible individuals exposed to a high risk of contagion, such as the prison community, allows obtaining optimal vaccination coverage and better results compared to vaccination carried out in the general population. This represents an opportunity to approach groups that, under normal conditions, have little contact with the health system. Therefore, it is of special interest to have data on vaccination coverage in prisons in order to prioritize interventions or reinforce vaccination schedules according to the intrinsic risk of each prison; reach as many susceptible people as possible by avoiding vaccinating people who have already been vaccinated or who have already suffered from the disease.The limitations of the study are mainly those derived from the heterogeneous methodology of the selected studies, since vaccine coverage data are not the main objective of some of them and interpretation of the data was made. This may at least in part explain some discrepancies in the results, when compared to the review by Madeddu et al.  LikewiseAll studies were carried out in industrialized countries, leaving major gaps in the available knowledge we have from prisons in developing countries.Prisoners are often an ignored and neglected population regarding public health policies at the international level. Harmonization of recommendations of vaccination strategies in prisons could be a fundamental step to improve access to health care, and for minimizing economic, organizational and disease burden in this setting.Vaccination strategies varied between countries and were often either targeting a specific vaccine-preventable disease or being implemented as part of an outbreak response. However, subsequent evaluations of the implemented interventions were not carried out systematically or are simply missing. Thus, these approaches may seem arbitrary and we were not able to evaluate whether specific interventions could have contributed to improve vaccination coverage and the overall health conditions of prisoners.


During the study timeframe, overweight and obesity prevalence, according to both the International Obesity Task Force and Orbegozo Foundation criteria, showed a downward trend. Differences in the anthropometric variables were observed from the beginning to the end of the study, mainly in girls. Analysis of the influence of the socioeconomic status revealed that children from families with lower incomes are in greater risk of suffering from overweight and obesity and showed lower effectiveness of the actions proposed by the program. The overall results of the study confirmed the effectiveness of community-based interventions in terms of childhood overweight/obesity prevention.Overweight and obesity amongst childhood are currently global health issues. However, this is the best stage of life to prevent diseases and to promote healthy habits. In our study, we evaluate the effectiveness of the THAO Salud Infantil, a community-based intervention program, by means of a cross-sectional study carried out from 2009 to 2019 surveying children aged 3 to 12 years old ( Estudio Nutricional de la Población Española) study revealed that overweight and obesity prevalence in Spanish populations aged 3 to 24 years exceeded 30%, whereas 16% were overweight and had concomitant abdominal obesity [Overweight and obesity in childhood and adolescence have recently became global health issues . Accordi obesity ,8,9, whi obesity  but also obesity . Moreove obesity .Overweight and obesity are the result of an imbalance between energy intake and expenditure that leads to positive energy balance being associated with lifestyle (activity level) and dietary intake . HoweverFleurbaix Laventie Ville Santé study carried out in France revealed that the implemented community-based intervention program led to less weight gain in the intervention towns than in the control town [Interestingly, schools play a key role in obesity prevention, owing to their long-term and in-depth contact with children. In fact, school environment, policies, curriculum, extra-curricular activities, and personnel may positively influence children’s lifestyle behaviors . In addirol town . Howeverrol town  showed tTHAO Salud Infantil Program is a community-based intervention program based on the Fleurbaix Laventie Ville Santé study (FLVS study) and carried out within the EPODE Program (Ensemble Prévenons l’Obesité Des Enfants) International Network (France). It is focused on the prevention of childhood obesity by means of the promotion of healthy life habits. It was developed by the THAO Foundation through the municipalities in order to promote healthy life habits in children aged 3 to 12 years [THAO Salud Infantil Program was implemented in 2007. However, the initially planned THAO Salud Infantil Program ended in 2016, even though Villanueva de la Cañada council continued it under the name of “Programa de prevención del sobrepeso y la obesidad-Estrategia NAOS en Villanueva de la Cañada”(Program for the prevention of overweight and obesity-NAOS strategy in Villanueva de la Cañada). Program implementation was led by the city council and included different intervention activities, such as monitoring of menus in school canteens, organization of healthy breakfasts and breaks, development of school gardens and implementation of other activities related to the heavy promotion of physical activity and the consumption of fruits and vegetables, among others.The 12 years . The THAn = 27,686) from state, charter and private schools in Villanueva de la Cañada . Specifically, volunteers were selected among the students of the indicated ages. The ethical approval was granted by the Clinical Research Ethics Committee of the CEU San Pablo University (Madrid) . Moreover, the study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Participants were informed about the goals of the study, and parental written consent on behalf of each participant was obtained prior to his or her inclusion in the study.This school-based cross-sectional study was carried out during academic years 2009–10, 2010–11, 2011–12, 2012–13, 2013–14, 2014–15, 2015–16, 2016–17, 2017–18 and 2018–19, surveying schoolchildren aged 3 to 12 years old of both genders  with an accuracy of 100 g, and height was measured to the nearest 0.5 cm using a stadiometer . Finally, waist circumference (WC) was measured with a flexible steel tape . All anthropometric measurements were made according to the recommendations of the International Standards for Anthropometric Assessment (ISAK)  by levelp < 0.05. All statistical analyses were performed using SPSS 24.0 Software .Results are presented as median (interquartile range) per group or as percentage. Variables were tested for normality using a Kolmogorov–Smirnov test. Non-parametric data were analyzed by the Kolmogorov–Smirnov test. Chi square test was used to compare the overweigh and obesity prevalence between years and type of school. Differences were considered significant at The study population included 27,686 children . The distribution of the study population in each academic year is shown in 2, respectively. No statistically significant differences were found in boys between anthropometric data at baseline and after the follow up, except for those aged 6, 7 and 12 years old (p ≤ 0.01 in boys aged 6 and p ≤ 0.05 in those aged 7 and 12) were determined between baseline and after 9-years follow up. Moreover, in boys aged 7 years, statistically significant differences were found for weight (p ≤ 0.05) at baseline and at the end of the study, whereas in those aged 12 years, significant differences were observed in WC at baseline and 9 years follow up (p ≤ 0.05). On the other hand, in girls . In addition, in girls aged 4 and 7 years, statistically significant differences in BMI and BMI z-score  were observed from the beginning to the end to the study.ears old , where sin girls , WC, weiAcross the study timeframe, the prevalence of overweight according to the IOTF reference values  tended tp ≤ 0.001), whereas the overweight and obesity prevalence in children decreased by 2.3% (p ≤ 0.05) and 1.4% (p ≤ 0.01), respectively  from 83.4% to 86.9%. In the total population, the prevalence of underweight slightly decreased from 0.8% in 2010 to 0.6% in 2019 . Of interest, this change was lower than the rise found in obesity.From children studied in 2010, according to OF criteria , 15.4% wp < 0.01) according to both criteria. However, no significant differences in underweight prevalence were determined based on OF criteria.p < 0.01). Regarding obesity, state schools showed significantly higher prevalence than charter schools and these, in turn, significantly higher obesity prevalence than private schools. However, in girls, according to the IOTF criteria, no significant differences between state and charters schools were found in terms of overweight prevalence, but when compared to full private schools, this was significantly lower. Nevertheless, obesity prevalence in girls based on the same criteria was significantly higher in state schools followed by charter and private schools, the ones with the lowest obesity rates. Data analysis according to OF criteria revealed that in boys, as observed before, normal weight prevalence in charter and private schools were significantly higher than that of state schools, whereas both overweight and obesity prevalence was higher in state schools than in private ones (p < 0.01). On the other hand, in girls by OF criteria, normal weight prevalence was significantly higher than that of charter schools and this, in turn, was significantly higher than that of state schools. The inverse trend was observed in terms of obesity prevalence, with the highest obesity prevalence observed in the public schools.Finally, the proportions of underweight, normal weight, overweight and obese children by school and stratified by sex are shown in Overweight and obesity have a multifactorial etiology involving genetic predisposition and multiple environmental factors, which include energy intake, activity level, composition of gut microflora, sedentary behavior, endocrine diseases, hydration status and/or socioeconomic position, among others ,13,14,15Nowadays, owing to the absence of a widely-shared consensus, it is highly recommended that prevalence studies consider several reference values , specifiOn the other hand, it is widely accepted that socioeconomic status plays an important role in overweight/obesity development ,34. SchoFurthermore, childhood is the best stage of life to prevent diseases and to promote healthy habits and, thus, the prevention of obesity is of major importance. However, socioeconomic status plays a crucial role that is important to consider. In fact, results of a longitudinal study carried out in Finland for over thirty years reported that higher socioeconomic status children in their adulthood showed healthier lifestyle patterns, including lower meat consumption, higher fish consumption, higher diet score and a higher physical activity index . Therefon = 27.686) as well as the long term follow up of the participants. Moreover, accredited anthropometrists (level I and II. ISAK) performed and collected the anthropometric measurements. However. the study also shows some limitations. For example, a limited amount of biological and behavioral variables were included as potential predictors of obesity development. Hence, we could not explore the influence of factors as maternal obesity, smoking at home, TV time, sleep duration, birth weight, breastfeeding and dietary and physical activity habits.The main strength of our study is the large sample size , in terms of childhood overweight/obesity prevention. Likewise, differences observed in prevalence according to children’s socioeconomic status confirmed the importance of health programs, especially in children from low-income families, owing to their great susceptibility to being overweight/obese. The latter may be of critical importance in a time of socioeconomical crisis associated with Covid-19 pandemic consequences.