Twice-daily PPI dosage improves outcomes among patients of eosinophilic esophagitis: Study

A recent study by Mayssan Muftah and colleagues explored the most effective dosing strategies for treating Eosinophilic Esophagitis (EoE) which is a chronic immune system disease that affects the esophagus. The key findings of this study were published in the American Journal of Gastroenterology.

Eosinophilic Esophagitis is marked by the accumulation of eosinophils in the esophagus that leads to inflammation, difficulty swallowing and food impaction. This comprehensive analysis involved a total of 305 newly diagnosed EoE patients and compared their histologic response rates among various dosing regimens of proton pump inhibitors (PPIs), a common treatment for the condition.

This study meticulously evaluated the effects of different PPI dosages including standard (omeprazole 20 mg daily), moderate (either 40 mg once daily or 20 mg twice daily) and high (40 mg twice daily) doses were administered over a period of at least 8 weeks. Remarkably, these findings reveal a significant disparity in the efficacy of treatment which highlights the superiority of twice-daily dosing over once-daily regimens.

About 42.3% of the patients achieved a histologic response to their PPI treatment with response rates that were markedly higher in the twice-daily groups. Also, 52.8% of the patients on the moderate twice-daily dose and 54.3% of the patients on the high twice-daily dose showed histologic improvement. In stark contrast, the once-daily dosing regimens (standard and moderate) had significantly lower response rates of 11.8% and 10%, respectively.

The multivariable analysis further illuminated the advantage of the twice-daily dosing schedule. The moderate twice-daily dose was associated with an adjusted odds ratio of 6.75 for achieving a histologic response. The high twice-daily dose had an even more pronounced effect with an adjusted odds ratio of 12.8. These statistics outcome suggest that patients who were receiving the twice-daily regimens were significantly more likely to express histological improvement by making a compelling case for revisiting current EoE treatment protocols.

This research illuminates the path forward for more effective management of Eosinophilic Esophagitis and also underlines the importance of dosage timing in the treatment regimen. Overall, these findings direct us to the potential of PPI for improved quality of life for EoE patients that offers promise for the individuals with this condition.

Reference:

Muftah, M., Goldin, A. H., Barshop, K., Hsu Blatman, K., Hamilton, M. J., Lo, W.-K., Hornick, J. L., & Chan, W. W. (2024). Twice-Daily Proton Pump Inhibitor Induces Higher Remission Rate in Eosinophilic Esophagitis Than Once-Daily Regimen Regardless of Total Daily Dose. In American Journal of Gastroenterology. Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.14309/ajg.0000000000002712

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Social Isolation Accelerates Biological Aging and Increases Mortality

A recent study conducted by researchers at Mayo Clinic sheds light on the detrimental effects of social isolation, revealing its association with accelerated biological aging and increased mortality risk. These findings underscore the importance of social connections in maintaining overall health and well-being. This study was published in the journal JACC Advances. The study was conducted by Rajai and colleagues.

Social isolation has long been recognized as a risk factor for various health issues, but its impact on biological aging and mortality risk has not been fully understood. This study aimed to examine the relationship between social contact and biological aging using advanced AI technology.

Researchers analyzed data from 280,000 adults aged 18 years and older who underwent outpatient care between June 2019 and March 2022. The study utilized an AI-enabled electrocardiogram (AI-ECG) to determine participants’ predicted biological age and assessed social isolation using the Social Network Index.

The key findings of the study were:

  • The study revealed that social isolation is associated with accelerated biological aging, as evidenced by a significant age gap between chronological and biological age.

  • Participants with lower Social Network Index scores, indicating greater social isolation, had a larger difference between chronological and biological age.

  • Social isolation was also linked to a higher risk of all-cause mortality, with participants who had low social index scores experiencing a significantly greater mortality risk.

  • Racial disparities were observed, with non-white participants showing a greater difference between chronological and biological age compared to white participants.

  • Comorbidities such as hypertension, hyperlipidemia, and diabetes were more prevalent among individuals with lower Social Network Index scores.

The study highlights the critical role of social connections in mitigating the effects of biological aging and reducing mortality risk. Addressing social isolation through interventions aimed at promoting social interaction and support networks could have significant implications for public health.

Social isolation is not only detrimental to mental well-being but also accelerates biological aging and increases mortality risk. Healthcare providers should consider screening for social isolation and implementing interventions to foster social connections, ultimately improving overall health outcomes and longevity.

Reference:

Rajai, N, Medina-Inojosa, J, Lewis, B. et al. Association Between Social Isolation With Age-Gap Determined by Artificial Intelligence-Enabled Electrocardiography. JACC Adv. null2024, 0 (0) .https://doi.org/10.1016/j.jacadv.2024.100890

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Study suggests protective effect of ergocalciferol on beta cells in new-onset type 1 diabetes

USA: A secondary analysis of a randomized clinical trial (RCT) published as a research letter in JAMA Network Open has shed light on the effect of ergocalciferol, an inactivated vitamin D analog, on β-cell function in new-onset type 1 diabetes (T1D).

The researchers showed that high-dose ergocalciferol, also known as vitamin D2, may help preserve β-cell function in kids with new-onset T1D and prolong the partial remission phase. 

In the study, ergocalciferol significantly reduced the ratio of fasting proinsulin to C-peptide (PI: C) and slowed the decrease in the percent change from baseline in the area under the curve (%∆AUC) of C-peptide among youths with type 1 diabetes.

The results suggest a protective action of ergocalciferol on β cells and possible mechanisms of action to prolong the partial remission (PR) phase of T1D. Ergocalciferol’s ∆ effect size for β-cell protection (15%) is comparable to that of verapamil, imatinib, and other agents (15%-19.4%). Thus, vitamin D may be combined with other treatments (eg, baricitinib and teplizumab) to prolong PR.

About 30% to 50% residual β-cell function may remain at the time of T1D diagnosis, and this may persist for months or years. A prolonged partial remission phase of T1D leads to decreased long-term complications and improved glycemic control. Previous studies have shown a significant decrease with ergocalciferol, in circulating tumor necrosis factor (TNF)-α and temporal trends in both hemoglobin A1c (HbA1c) and insulin dose–adjusted A1c (IDAA1c), a marker of PR, compared with placebo.

Benjamin Udoka Nwosu, Cohen Children’s Medical Center, New Hyde Park, New York, and colleagues report the effect size of high-dose ergocalciferol (50 000 IU/wk for two months, then biweekly for ten months) versus placebo on β-cell function, denoted by the ratio of fasting proinsulin to C-peptide and the percent change from baseline in the area under the curve of C-peptide.

For this purpose, the researchers conducted a post hoc secondary analysis of a double-blind, single-center, placebo-controlled, parallel-group randomized clinical trial of ergocalciferol vs placebo in youths (aged 10-21 years) with newly diagnosed T1D. They obtained written informed consent from adults and parents and assent from youths (aged <18 years). The study followed the CONSORT reporting guideline.

Exclusion and inclusion criteria included fasting C-peptide (>0.1 nmol/L) or stimulated C-peptide (≥0.2 nmol/L) and a positive diabetes-associated autoantibody profile. Participants entered a run-in phase of 1 to 2 months, maintained a treat-to-target insulin regimen, and were randomized to ergocalciferol or placebo. Participants completed mixed-meal tolerance tests to estimate fasting glucose, C-peptide, and proinsulin (normal range, 3.6-22 pmol/L) at 0, 3, 6, 9, and 12 months.

Of 48 youths with type 1 diabetes eligible for the 12-month trial, 36 were randomized to ergocalciferol or placebo. Their mean age was 13.5 years.

Based on the analysis, the researchers reported the following findings:

  • Ergocalciferol significantly decreased fasting PI: C vs placebo (mean [SE], −0.0009 versus 0.0011) for the monthly overall difference in trends.
  • · The mean decrease in %∆AUC C-peptide was similar for both groups in the first three months (−10.9 versus −8.2) but subsequently decreased more slowly with ergocalciferol vs placebo (−28.4 versus −41.5), with a significant reduction in monthly overall temporal trends (mean [SE], −2.8% vs −4.7 %).

“Although this RCT was limited by its single-center setting, the results suggest a protective action of ergocalciferol on β cells and possible mechanisms of action to prolong PR,” the researchers concluded.

Reference:

Nwosu BU, Parajuli S, Sharma RB, Lee AF. Effect of Ergocalciferol on β-Cell Function in New-Onset Type 1 Diabetes: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(3):e241155. doi:10.1001/jamanetworkopen.2024.1155

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Sweeteners don’t increase appetite, suggests new evidence from randomised controlled trial

Replacing sugar with artificial and natural sweeteners in foods does not make people hungrier-and also helps to reduce blood sugar levels, a significant new study has found.

The double blind randomised controlled trial found that consuming food containing sweeteners produced a similar reduction in appetite sensations and appetite-related hormone responses as sugary foods – and provides some benefits such as lowering blood sugar, which may be particularly important in people at risk of developing type 2 diabetes.

The use of sweeteners in place of sugar in foods can be controversial due to conflicting reports about their potential to increase appetite. Previous studies have been carried out but did not provide robust evidence.

However, the researchers say their study, which meets the gold standard level of proof in scientific investigation, provides very strong evidence that sweeteners and sweetness enhancers do not negatively impact appetite and are beneficial for reducing sugar intake.

The trial was led by the University of Leeds in collaboration with the The Rhône-Alpes Research Center for Human Nutrition. It is the latest study to be published by the SWEET consortium of 29 European research, consumer and industry partners which is working to develop and review evidence on long term benefits and potential risks involved in switching over to sweeteners and sweetness enhancers in the context of public health and safety, obesity, and sustainability. It was funded by Horizon Europe.

Lead author Catherine Gibbons, Associate Professor in the University of Leeds’ School of Psychology, said: “Reducing sugar consumption has become a key public health target in the fight to reduce the rising burden of obesity-related metabolic diseases such as type 2 diabetes.

“Simply restricting sugar from foods without substitution may negatively impact its taste or increase sweet cravings, resulting in difficulties sticking to a low-sugar diet. Replacing sugars with sweeteners and sweetness enhancers in food products is one of the most widely used dietary and food manufacturing strategies to reduce sugar intake and improve the nutritional profile of commercial foods and beverages.”

Principal investigator Graham Finlayson, Professor of Psychobiology in the University of Leeds’ School of Psychology, said: “The use of sweeteners and sweetness enhancers has received a lot of negative attention, including high profile publications linking their consumption with impaired glycaemic response, toxicological damage to DNA and increased risk of heart attack and stroke. These reports contribute to the current befuddlement concerning the safety of sweeteners and sweetness enhancers among the general public and especially people at risk of metabolic diseases.

“Our study provides crucial evidence supporting the day-to-day use of sweeteners and sweetness enhancers for body weight and blood sugar control.”

The study, which is the first of its kind, looked at the effects of consuming biscuits containing either sugar or two types of food sweetener: natural sugar substitute Stevia, or artificial sweetener Neotame on 53 adult men and women with overweight or obesity.

Until now, virtually all studies of the effects of sweeteners and sweetness enhancers on appetite and glycaemia have been conducted using beverages as the vehicle. Few studies include volunteers with overweight or obesity and few have included volunteers of both sexes.

Most studies have only compared a single sweetener, mostly aspartame, with a control, and very few studies have examined the effect of repeated daily intake of a known sweetener or sweetness enhancer in the normal diet.

The new trial took place at the University of Leeds and the Rhône-Alpes Research Center for Human Nutrition (CRNH-RA), France between 2021 and 2022. Participants were all aged 18 to 60, with overweight or obesity.

The trial consisted of three two-week consumption periods, where participants consumed biscuits with either fruit filling containing sugar; natural sugar substitute Stevia, or artificial sweetener Neotame, each separated by a break of 14-21 days. Day 1 and day 14 of the consumption periods took place in the lab.

Participants were instructed to arrive in the lab after an overnight fast, a blood sample was taken to establish baseline levels of glucose, insulin and appetite-related hormones. They were also asked to rate their appetite and food preferences.

After consuming the biscuits, they were asked to rate how full they felt over several hours. Glucose and insulin levels were measured, as were ghrelin, glucagon-like peptide 1 and pancreatic polypeptide – hormones associated with the consumption of food.

The results from the two sweetener types showed no differences in appetite or endocrine responses compared to sugar, but insulin levels measured over two hours after eating were reduced, as were blood sugar levels.

SWEET project joint co-ordinator Professor Anne Raben, from the University of Copenhagen, Denmark, said: “The findings show that sweeteners are a helpful tool to reduce intake of added sugar without leading to a compensatory increase in appetite or energy intake, thereby supporting the usefulness of sweeteners for appetite, energy and weight management.” 

Reference:

Catherine Gibbons, Kristine Beaulieu, Eva Almiron-Roig, Santiago Navas-Carretero, J. Alfredo Martínez l, Beverley O’Hara, Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity—a randomised crossover trial from the SWEET consortium, EBioMedicine, DOI:https://doi.org/10.1016/j.ebiom.2024.105005.

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Study reveals bidirectional link between premenstrual disorders and perinatal depression

A study from Karolinska Institutet published in the journal PLOS Medicine has revealed a bidirectional link between premenstrual disorders and perinatal depression.

Acccording to the  study,  Women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) have a higher risk of perinatal depression. Conversely, women with perinatal depression have a higher risk of developing premenstrual disorders.

Premenstrual disorders like PMS or PMDD and perinatal depression are similar in the way that symptoms appear in connection with hormonal changes. This fact has given rise to the hypothesis that the disorders share both causes and risk factors. Now a study by researchers at Karolinska Institutet shows a bidirectional association between premenstrual disorders and perinatal depression.

“We can show that women with PMS or PMDD have a higher risk of developing perinatal depression and vice versa,” says Qian Yang, affiliated researcher at the Institute of Environmental Medicine, Karolinska Institutet and one of the main authors of the paper. “The results support the hypothesis that the diseases might have common causes.”

Between 2001 and 2018, approximately 1,800,000 pregnancies were registered in the Swedish Medical Birth Register. Among these, the researchers were able to identify nearly 85,000 women who suffered from perinatal depression. Additional national registers, such as the patient register and the drug register, were also used to identify women diagnosed with PMS or PMDD. These were then compared to a control group of nearly 850,000 birthing women who did not develop perinatal depression during the same period.

The results showed that women with premenstrual disorders were five times more likely to experience perinatal depression. Conversely, women who experienced perinatal depression were twice as likely to develop premenstrual disorders.

The bidirectional association was noted for both prenatal and postnatal depression, regardless of history of psychiatric disorders.

“It is important that healthcare professionals who meet with women during pregnancy are aware of the link between premenstrual disorders and perinatal depression in order to provide well-informed advice,” says Donghao Lu, Associate Professor at the Institute of Environmental Medicine, Karolinska Institutet and last author of the paper.

The authors emphasize that more research is needed to understand the biological link between premenstrual disorders and perinatal depression. In addition, more information is needed to clarify whether the association also applies to women with mild PMS or perinatal depression.

Reference:

Qian Yang ,Emma Bränn,Elizabeth R. Bertone- Johnson,Arvid Sjölander,Fang Fang,Anna Sara Oberg,Unnur A. Valdimarsdóttir,Donghao Lu, The bidirectional association between premenstrual disorders and perinatal depression: A nationwide register-based study from Sweden, PLoS Medicine, https://doi.org/10.1371/journal.pmed.1004363.

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Bone scintigraphy combined with integrated SPECT/CT advantageous in differentiating prosthetic infection from loosening: study

Prosthetic loosening and infection are still common complications after joint replacement. Over the past few years, single-photon emission computed tomography–computed tomography (SPECT/CT) was widely used and showed unique value based on the combination of anatomic and metabolic information of foci. However, its performance in differentiating between prosthetic loosening and periprosthetic infection after joint replacement is still the focus of clinicians and deserves further investigation.

Yaxin Tian et al conducted a retrospective study to determine whether bone scintigraphy combined with SPECT/CT still can differentiate prosthetic infection from loosening in patients after joint replacement. The differential efficacy in hip and knee prosthesis was also analyzed. Blood biomarkers for the diagnosis of periprosthetic infection were also evaluated.

The study was conducted at Ningxia Medical University, Yinchuan, China. It was published in “Indian Journal of Orthopaedics.”

Data sets of 74 prosthetic joints (including knees and hips), with suspected prosthetic loosening or infection were evaluated. Besides the results of nuclear imaging, X-ray images and serum biomarker were also recorded. Telephone follow-up and revision surgery after SPECT/CT were used as a gold standard. The sensitivity and accuracy of different imaging modalities were calculated by Chi-square test. The diagnostic efficacy of imaging methods and serum biomarkers were then analyzed by the area under curve (receiver operating characteristic curves, ROC) in SPSS 26.

The key findings of the study were:

• In all, 47 joints (14 knees and 33 hips) were confirmed as aseptic loosening, while 25 joints (18 knees and 7 hips) were confirmed as infection.

• The sensitivity and accuracy of SPECT combined with SPECT/CT imaging were the highest (92.86% and 87.84%, respectively).

• The differential efficacy of bone scintigraphy combined with SPECT/CT imaging was also better than any other single imaging modality.

• In the analysis of involved prosthesis, prosthetic loosening occurred more in hip prosthesis and knee prosthesis was easily infected (P<0.05).

• The sensitivity of ESR and CRP were 80% and 84%, respectively.

The authors concluded – “Bone scintigraphy with hybrid SPECT/CT remains encouraging in differentiating prosthetic infection from loosening after joint replacement. The diagnostic efficacy of differentiation in hip prosthesis was better than knee. Serum biomarkers cannot be used alone to differentiate prosthetic infection from loosening.”

Further reading:

Can99mTc MDP–SPECT/CT Differentiate Loosening and Infection After Hip and Knee Replacements?

Yaxin Tian, Yanghongyan Jiang et al

Indian Journal of Orthopaedics (2024) 58:316–322

https://doi.org/10.1007/s43465-024-01095-6

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No increased risk of stroke in older adults who received COVID-19 bivalent vaccine: JAMA

USA: In a self-controlled case series of 11,000 Medicare beneficiaries age 65 or older, the primary analysis showed no evidence of a significantly increased risk of stroke during the days immediately following the administration of either brand of the COVID-19 bivalent vaccine.

“In the Medicare beneficiaries who experienced stroke following the administration of either brand of the COVID-19 bivalent vaccine, the stroke risk was not significantly increased during the 1- to 21-day or 22- to 42-day risk window after vaccination compared with the 43- to 90-day control window,” the researchers reported. The findings were published online in the Journal of the American Medical Association (JAMA) on March 19, 2024.

In January 2023, the US Food and Drug Administration and the US Centers for Disease Control and Prevention raised a safety concern for ischemic stroke among adults aged 65 years or above who received the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine.

Against the above background, Yun Lu, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, and colleagues aimed to evaluate stroke risk after administering(1) either brand of the COVID-19 bivalent vaccine, (2) either brand of the COVID-19 bivalent plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant administration) and (3) a high-dose or adjuvanted influenza vaccine.

For this purpose, the researchers conducted a self-controlled series including 11 001 Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine (among 5 397 278 vaccinated individuals). The study period was 2022 through 2023.

The main outcomes were stroke risk (transient ischemic attack, non-hemorrhagic stroke, combined outcome of transient ischemic attack or non-hemorrhagic stroke, or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day risk window following vaccination versus the 43- to 90-day control window.

The researchers reported the following findings:

  • 5 397 278 Medicare beneficiaries received either brand of the COVID-19 bivalent vaccine (median age, 74 years; 56% were women).
  • Among the 11 001 beneficiaries who experienced a stroke after receiving either brand of the COVID-19 bivalent vaccine, there were no statistically significant associations between either brand of the COVID-19 bivalent vaccine and the outcomes of transient ischemic attack, non-hemorrhagic stroke, non-hemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke during the 1- to 21-day or 22- to 42-day risk window vs the 43- to 90-day control window.
  • Among the 4596 beneficiaries who experienced a stroke after concomitant administration of either brand of the COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and non-hemorrhagic stroke during the 22- to 42-day risk window for the fizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine and a statistically significant association between vaccination and transient ischemic attack during the 1- to 21-day risk window for the Moderna mRNA-1273.222 COVID-19 bivalent vaccine.
  • Among the 21 345 beneficiaries who experienced stroke after administration of a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and non-hemorrhagic stroke during the 22- to 42-day risk window.

In conclusion, there was no evidence of a significantly increased risk for stroke during the days immediately after vaccination among Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine.

Reference:

Lu Y, Matuska K, Nadimpalli G, et al. Stroke Risk After COVID-19 Bivalent Vaccination Among US Older Adults. JAMA. 2024;331(11):938–950. doi:10.1001/jama.2024.1059

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Obesity in childhood may double risk of developing multiple sclerosis in early adulthood, shows study

New research to be presented at this year’s European Congress on Obesity in Venice, Italy (12-15 May) shows that having obesity in childhood is associated with a more than doubling of the risk of later developing multiple sclerosis. The study is by Professor Claude Marcus and Associate Professor Emilia Hagman, Karolinska Institutet, Stockholm, Sweden, and colleagues.

Emerging evidence implies a link between high BMI in adolescence and an increased risk of Multiple Sclerosis (MS). Yet, most studies evaluating this association are cross-sectional, have retrospective design with self-reported data, have used solely genetic correlations, or use paediatric weight data before the obesity epidemic. Therefore, to authors aimed to prospectively evaluate the risk of developing MS in a large cohort of patients with paediatric obesity compared with the general population.

They included patients aged 2 – 19 years with obesity enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) between 1995 – 2020, and a matched comparison group from the general population. Matching criteria included sex, year of birth, and residential area. Exclusion criteria were secondary obesity (eg brain tumours such as craniopharyngioma), and genetic syndromes (eg Prader Willi, morbus Down), and MS diagnosis before 15 years of age (that is, already developing in childhood). MS was identified through Sweden’s National Patient Register. Individuals were followed from obesity treatment initiation, or from 15 years of age if treatment was initiated earlier, until MS diagnosis, death, emigration, or August 2023, whichever came first. The authors computer and statistical modelling to calculate any potential association. Due to previous reported genetic associations of MS, the authors also assessed levels of parental MS which was present in 0.99% in the obesity cohort and 0.68% in the general population comparators.

The data included 21 661 patients (54% boys) from the paediatric obesity cohort with a median age of obesity treatment initiation (behaviour and lifestyle modification) of 11.4 years (years and 102 230 general population comparators. The median follow-up time was 5.6 years, corresponding to median age of 20.8 years in the follow-up population (and 50% of the population were aged between 18 and 25 at the point analysis, with the highest age in the cohort 45 years).

During follow-up, 0.13% [n=28, 18 (64%) female, 10 (36%) male] developed MS in the obesity cohort, whereas the corresponding number in the general population was 0.06% [n=58, 38 (66%) female, 20 (34%) male]. The mean (SD) age of MS diagnosis was comparable between the groups; 23.4 years in the obesity cohort versus 22.8 years in the general population comparators. (see graph in full abstract). The small numbers who developed MS so far means that the study was not sufficiently statistically powered to state the increased risk to females developing MS – however the results follow the general increased risk to females (the estimate ratio of female: male affected by MS in the general population is 4:1).

The crude incidence rate of MS per 100 000 person years was 19.3 in the obesity cohort and 8.3 in the general population cohort. Analyses adjusted for presence of parental MS (heredity) (which was more prevalent in the obesity cohort, as above) revealed that the risk of developing MS was more 2.3 times higher than in the paediatric obesity cohort, with both these findings statistically significant.

The authors say: “Despite the limited follow-up time, our findings highlight that obesity in childhood is associated with an increased susceptibility of early-onset MS more than two-fold. Given that paediatric obesity is prevalent, it is likely to serve as a critical etiological contributor to the escalating prevalence of MS. Paediatric obesity is associated with several autoimmune diseases and the leading hypothesis is that the persistent low-grade inflammatory state, typically observed in obesity, is mediating the association. Understanding these pathways is crucial for developing targeted prevention and intervention strategies to normalise the risk for MS in children and adolescents with obesity.”

They add: “There are several studies showing that MS has increased over several decades and obesity is believed to be one major driver for this increase. Thanks to our prospective study design, we can confirm this theory.”*

“Even though the risk for MS is more than double among children and adolescence with obesity, the absolute risk for MS remains lower than for many other comorbidities associated with obesity. Nevertheless, our study adds to the evidence that obesity in early life increases the risk for a plethora of diseases including MS, and not only the well-known cardiometabolic conditions such as heart disease and diabetes.”

Reference:

Study shows obesity in childhood associated with a more than doubling of risk of developing multiple sclerosis in early adulthood, European Association for the Study of Obesity, Meeting: European Congress on Obesity (ECO2024).

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Passive smoking during pregnancy tied to increased risk of atopic dermatitis in offspring: Study

China: A recent meta-analysis published in the Journal of the European Academy of Dermatology and Venereology has shown an association between passive smoking during pregnancy and an increased risk of eczema development in offspring.

Atopic dermatitis (eczema), a condition that causes dry, itchy, and inflamed skin, is common worldwide. Several studies have explored the modifiable factors of atopic dermatitis (AD), including smoking. The adverse effects of smoking on asthma have been well documented in adolescents, however, the implications of smoking on atopic dermatitis are controversial.

The findings are contradictory and could be due to disparities in study design and covariables adjusted for in the analysis. For instance, the results of a few prospective cohort studies, which reported non-significant or negative correlations between atopic dermatitis and passive smoking, may have exhibited selection bias due to the inclusion of restricted residential regions and a lack of compliance with the survey or involving a small study population. Additionally, because AD generally develops in young individuals and it is rare for children to smoke, the focus of the majority of studies has been the effects of passive smoking on atopic dermatitis in children

Against the above background, Wenjie Ren, School of Public Health, Xinxiang Medical University, Xinxiang, China, and colleagues examine the evidence of the relationship between active smoking or passive smoking during pregnancy and atopic dermatitis (AD) in offspring.

For this purpose, the protocol was written following the PRISMA Checklist and was registered in the PROSPERO database. The researchers searched online databases to identify all potentially related articles from inception through 1 December 2022. Cohort and case–control studies were assessed using the Newcastle–Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) critical appraisal tool was used to assess the quality of cross-sectional studies.

Heterogeneity was determined using Cochrane Q tests and I2 statistics. Additionally, the reasons for the heterogeneity were analyzed according to the population source, research design, and population size. Fifteen observational studies were included in the analysis.

“Our meta-analysis suggests that atopic dermatitis in offspring is not associated with active smoking during pregnancy (pooled OR, 0.96), however, it is related to passive smoking (OR, 1.52),” the researchers reported.

“Passive smoking during pregnancy is associated with an increased risk of eczema development in offspring.”

“More research is required to explore the risk of active smoking and atopic dermatitis development in offspring, particularly the association between measurements of pregnancy cotinine levels in maternal body fluids and AD in offspring,” they concluded.

Reference:

Chao, L., Liang, W., Zhao, X., Liang, Z., Wu, W., Song, J., & Ren, W. Maternal tobacco exposure during pregnancy and atopic dermatitis in offspring: A systematic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology. https://doi.org/10.1111/jdv.19958

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Surgical nerve decompression tied to reduced pain in patients with diabetic neuropathy: Study

USA: A recent five-year study published in the Annals of Surgery has shed light on the effect of lower extremity nerve decompression in patients with painful diabetic peripheral neuropathy (DPN). 

“Although nerve decompression was tied to reduced pain, the benefit of surgical decompression requires further investigation since a placebo effect may be responsible for part or all of these effects,” the researchers wrote. 

Surgical nerve decompression, used to treat conditions such as carpal tunnel syndrome and sciatica, could play a role in relieving the pain of diabetic neuropathy patients, researchers at UT Southwestern Medical Center found.

The five-year study, published in the Annals of Surgery, was the first randomized control trial to assess the effectiveness of lower extremity nerve decompression surgery on patients with diabetic peripheral neuropathy.

Approximately 20 million Americans suffer from diabetic neuropathy, a progressive condition that damages the nerves, primarily in the legs and feet. The primary treatment today is the use of temporary pain-relieving medications, but many patients find them ineffective after prolonged use.

“Diabetic neuropathy can be debilitating, leading to a lack of mobility and a severe reduction in quality of life,” said study leader Shai Rozen, M.D., Professor and Vice Chair of Plastic Surgery. “It’s believed that roughly one-third of those with neuropathy pain have nerve compression – where there is direct and chronic pressure on a peripheral nerve – due to physiological changes brought on by diabetes. Our research suggests that nerve decompression surgery to release compressed nerves from surrounding tissue could offer lasting relief for those individuals.”

In diabetic neuropathy, nerves can swell and eventually be compressed by surrounding semirigid tissue, causing pain, muscle weakness, or both. In the surgery, the semirigid tissue is removed from the swollen nerve, allowing for improved blood flow to relieve symptoms.

The study followed 78 patients at UT Southwestern and Parkland Health who were randomly placed into two groups-one receiving surgery and one serving as an observation group who remained on medication only. Those selected for surgery also had one leg randomly chosen for “sham surgery”-when the surgeon makes incisions to mimic the procedure but without principal therapeutic actions (i.e., nerve release)-while the other leg underwent nerve decompression.

Patients agreed to being blinded about which leg underwent sham surgery and which had decompression surgery. Additionally, the evaluators were blinded regarding which group the patients were in. “This masking of patients and evaluators further increases the reliability of the results,” Dr. Rozen said.

During follow-up visits, patients completed standard pain and lifestyle questionnaires. At the 12-month visit, the patients who underwent surgical intervention reported significantly less pain in both legs, while the observation group’s pain rankings were unchanged.

At 56 months, under the same patient- and evaluator-blinded conditions, the surgical group reported even greater pain reduction, while the observation group had worse pain. Unlike the 12-month follow-up, however, surgical patients reported far more improvement in their decompressed legs than in their sham surgery legs.

“The one-year reports of pain improvement in both legs could mean that there is a placebo effect taking place, but the five-year results suggest that the procedure actually does have a positive long-term impact on pain,” Dr. Rozen said. “There is still much debate in the medical community about the value of decompression surgery in treating diabetic neuropathy, and while this study doesn’t settle the issue, it should help expand the discourse among stakeholders and hopefully lead to even more research. The goal is to better understand the efficacy of nerve decompression surgery on diabetic neuropathy and improve our ability to identify patients who are likely to respond to surgical intervention.” 

Reference:

Rozen, Shai M. MD*; Wolfe, Gil I. MD†; Vernino, Steven MD, PhD‡; Raskin, Philip MD§; Hynan, Linda S. PhD∥,¶; Wyne, Kathleen MD, PhD#; Fulmer, Rita FNP-BC**; Pandian, Geetha MD**; Sharma, Shiv K. MD††; Mohanty, Ahneesh J. MD‡‡; Sanchez, Cristina V. BS*; Hembd, Austin MD*; Gorman, April PhD∥. Effect of Lower Extremity Nerve Decompression in Patients with Painful Diabetic Peripheral Neuropathy: The DNND Randomized, Observation Group- and Placebo Surgery-controlled Clinical Trial. Annals of Surgery ():10.1097/SLA.0000000000006228, February 8, 2024. | DOI: 10.1097/SLA.0000000000006228

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