Pelvic organ prolapse: self-management of pessaries can be a good option.

The studyHagen S, Kearney R, Goodman K, et al. Clinical effectiveness of vaginal pessary self-management vs clinic-based care for pelvic organ prolapse (TOPSY): a randomised controlled superiority trial. eClinicalMedicine 2023;66:102326.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/pelvic-organ-prolapse-self-management-of-pessaries-can-be-a-good-option/.

How common are side effects of treatment to prevent gout flares when starting allopurinol?

The studyRoddy E, Bajpai R, Forrester H, et al. Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink. Ann Rheum Dis 2023;82:1618-25.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/how-common-are-side-effects-of-treatment-to-prevent-gout-flares-when-starting-allopurinol/.

Even short periods of diabetes remission are linked to lower risk of heart attack and stroke.

The studyDambha-Miller H, Hounkpatin HO, Stuart B, Farmer A, Griffin S. Type 2 diabetes remission trajectories and variation in risk of diabetes complications: a population-based cohort study. PLoS ONE 2023;18. doi:10.1371/journal.pone.0290791To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/even-short-periods-of-diabetes-remission-are-linked-to-lower-risk-of-heart-attack-and-stroke/.

Early, intense therapy for language problems after a stroke is linked to the greatest benefits.

The studyBrady MC, Ali M, VandenBerg K, et al. Complex speech-language therapy interventions for stroke-related aphasia: the RELEASE study incorporating a systematic review and individual participant data network meta-analysis. Health Social Care Delivery Res 2022;10.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/therapy-for-language-problems-after-a-stroke-is-most-effective-when-given-early-and-intensively/.

Weight regain does not eliminate the long term benefits of weight management programmes.

The studyHartmann-Boyce J, Theodoulou A, Oke JL, et al. Long term effect of weight regain following behavioral weight management programs on cardiometabolic disease incidence and risk: systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2023;16:263-76.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/weight-regain-does-not-eliminate-the-long-term-benefits-of-weight-management-programmes/#:~:text=Study%20author&text=Many%20people%20believe%20that%20if,been%20the%20case%20without%20it.

What are the chances of having a second epileptic seizure?

The studyNeligan A, Adan G, Nevitt SJ, et al. Prognosis of adults and children following a first unprovoked seizure. Cochrane Database Syst Rev 2023;1:1-75.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/epilepsy-what-are-the-chances-of-having-a-second-seizure/.

How to reduce medications for people with multiple long term conditions.

The studyReeve J, Maden M, Hill R, et al. Deprescribing medicines in older people living with multimorbidity and polypharmacy: the TAILOR evidence synthesis. Health Technol Assess 2022;26:1-148.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/how-to-safely-deprescribe-medications-for-people-with-multiple-long-term-conditions/.

Male sling is as good as more complex surgery for incontinence after prostate surgery.

The studyConstable L, Abrams P, Cooper D, et. Synthetic sling or artificial urinary sphincter for men with urodynamic stress incontinence after prostate surgery: the MASTER non-inferiority RCT. Health Technol Assess 2022;26:1-152To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/male-sling-is-as-good-as-more-complex-surgery-for-incontinence-after-prostate-surgery/.

One-stage hip revisions are as good as two-stage surgery to replace infected artificial hips.

The studyBlom AW, Lenguerrand, Strange S, et al. Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial. BMJ 2022;379:e071281.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/one-stage-hip-revisions-are-as-good-as-2-stage-surgery-to-replace-infected-artificial-hips/.

Assisted vaginal births: women who tear or have a surgical cut need prompt antibiotics.

The studyHumphries ABC, Linsell L, Knight M. Factors associated with infection after operative vaginal birth-a secondary analysis of a randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth. AJOG 2023;228:328.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/assisted-vaginal-births-women-need-prompt-antibiotics/.

One-session treatment is as effective as multi-session therapy for young people with phobias.

The studyWright B, Tindall L, Scott AJ, et al. One-session treatment compared with multisession CBT in children aged 7-16 years with specific phobias: the ASPECT non-inferiority RCT. Health Technol Assess 2022;26:1-174.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/one-session-cbt-treatment-effective-for-young-people-with-phobias/.

Combination therapy for painful diabetic neuropathy is safe and effective.

The studyTesfaye S, Sloan G, Petrie J, et al. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial. Lancet 2022;400:680-90.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/combination-therapy-for-painful-diabetic-neuropathy-is-safe-and-effective/.

Online cognitive behavioural therapy for post-traumatic stress disorder is as effective as face-to-face therapy.

The studyBisson JI, Ariti C, Cullen K, et al. Guided, internet based, cognitive behavioural therapy for post-traumatic stress disorder: pragmatic, multicentre, randomised controlled non-inferiority trial (RAPID). BMJ 2022;377:e069405.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/online-cbt-for-ptsd-is-as-effective-as-face-to-face-therapy/.

Routine follow-up may not be needed for people undergoing joint replacement surgery.

The studyKingsbury SR, Smith LK, Czoski Murray CJ, et al. Safety of disinvestment in mid- to late-term follow-up post primary hip and knee replacement: the UK SAFE evidence synthesis and recommendations. Health Soc Care Deliv Res 2022;10. doi:10.3310/KODQ0769To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/joint-replacement-many-people-can-safely-wait-10-years-for-follow-up/.

Methenamine is as effective as antibiotics at preventing urinary tract infections.

The studyHarding C, Mossop H, Homer T, et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial. BMJ 2022;376:e068229.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/methenamine-as-good-as-antibiotics-preventing-urinary-tract-infections/.

Maternal behaviours and adult offspring behavioural deficits are predicted by maternal TNFα concentration in a rat model of neurodevelopmental disorders.

Exposure to inflammatory stressors during fetal development is a major risk factor for neurodevelopmental disorders (NDDs) in adult offspring. Maternal immune activation (MIA), induced by infection, causes an acute increase in pro-inflammatory cytokines which can increase the risk for NDDs directly by inducing placental and fetal brain inflammation, or indirectly through affecting maternal care behaviours thereby affecting postnatal brain development. Which of these two potential mechanisms dominates in increasing offspring risk for NDDs remains unclear. Here, we show that acute systemic maternal inflammation induced by the viral mimetic polyinosinic:polycytidylic acid (poly I:C) on gestational day 15 of rat pregnancy affects offspring and maternal behaviour, offspring cognition, and expression of NDD-relevant genes in the offspring brain. Dams exposed to poly I:C elicited an acute increase in the pro-inflammatory cytokine tumour necrosis factor (TNF; referred to here as TNFα), which predicted disruption of key maternal care behaviours. Offspring of poly I:C-treated dams showed early behavioural and adult cognitive deficits correlated to the maternal TNFα response, but, importantly, not with altered maternal care. We also found interacting effects of sex and treatment on GABAergic gene expression and DNA methylation in these offspring in a brain region-specific manner, including increased parvalbumin expression in the female adolescent frontal cortex. We conclude that the MIA-induced elevation of TNFα in the maternal compartment affects fetal neurodevelopment leading to altered offspring behaviour and cognition. Our results suggest that a focus on prenatal pathways affecting fetal neurodevelopment would provide greater insights into the mechanisms underpinning the TNFα-mediated genesis of altered offspring behaviour and cognition following maternal inflammation.

Hospital policies can create barriers to good management of opioid withdrawal.

The studyHarris M, Holland A, Lewer D, et al. Barriers to management of opioid withdrawal in hospitals in England: a document analysis of hospital policies on the management of substance dependence. BMC Med 2022;20:151.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/many-hospital-policies-create-barriers-to-good-management-of-opioid-withdrawal/.

How to improve discussions about osteoarthritis in primary care.

The studyVennik J, Hughes S, Smith KA, et al. Patient and practitioner priorities and concerns about primary healthcare interactions for osteoarthritis: a meta-ethnography. Patient Educ Couns 2022;105:1865-77.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/discussions-about-osteoarthritis-in-primary-care/.

Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity.

In response to physical exercise and diet, skeletal muscle adapts to energetic demands through large transcriptional changes. This remodelling is associated with changes in skeletal muscle DNA methylation which may participate in the metabolic adaptation to extracellular stimuli. Yet, the mechanisms by which muscle-borne DNA methylation machinery responds to diet and exercise and impacts muscle function are unknown. Here, we investigated the function of de novo DNA methylation in fully differentiated skeletal muscle. We generated muscle-specific DNA methyltransferase 3A (DNMT3A) knockout mice (mD3AKO) and investigated the impact of DNMT3A ablation on skeletal muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3A reduced DNA methylation in skeletal muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation, but did not affect exercise capacity and whole-body energy metabolism compared to wild type mice. Loss of DNMT3A did not alter skeletal muscle mitochondrial function or the transcriptional response to exercise however did influence the expression of genes involved in muscle development. These data suggest that DNMT3A does not have a large role in the function of mature skeletal muscle although a role in muscle development and differentiation is likely.