Cervical cancer screening integrated in routine clinical care of women living with HIV.

OBJECTIVE: To evaluate if integrated cervical cancer screening (CCS) for women living with HIV (WLWH) in routine HIV care resulted in increased adherence to screening, and to describe the prevalence of Human Papillomavirus (HPV)-specific genotypes and the incidence of cellular abnormalities. DESIGN: Cohort study. METHODS: WLWH who accepted the offer of combined CCS and HIV care (Group 1), WLWH who declined the offer (Group 2), and WLWH not offered CCS within HIV care (Group 3) between 2013-2019 were included. Data was collected from The Danish HIV Cohort Study and The Danish Pathology Data Bank. Adherence to the CCS program was defined as fulfilled if WLWH were screened annually. RESULTS: A total of 804 WLWH were included. WLWH who accepted CCS within HIV care (group 1; n = 218) had significantly higher adherence to screening in all study years 22-99% compared to the WLWH who declined CCS (group 2; n = 232) 10-16% and WLWH who were not invited for CCS (group 3; n = 354) 11-25%. There was no significant difference in the prevalence of HPV-specific genotypes and incidence of cellular abnormalities among the three groups. CONCLUSION: Integrating CCS for WLWH in routine HIV care resulted in higher adherence to the CCS guidelines. Combined services thereby represent an opportunity to engage WLWH in HIV care into preventive services.

Development of a Novel Prediction Tool for Response to First-Line Treatments of Monosymptomatic Nocturnal Enuresis-A Randomized, Controlled International Multicenter Study (DRYCHILD).

PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. MATERIALS AND METHODS: A randomized, controlled, international multicenter study was conducted in 324 treatment-naïve children (6-14 years) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated. RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (RR = 1.21 (1.02-1.45), P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (RR = 1.46 (1.14-1.87), P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (ROC 0.85). CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improve response to first line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response.

Discontinuing absorbent pants in children with bedwetting: a randomized controlled trial.

The objective of this study is to examine the effect of discontinuing wearing protective garments (absorbent pyjama pants - APP) in children with severe childhood nocturnal enuresis (NE). The study employs a multicenter, parallel, randomized controlled trial. Following a 4-week run-in period, participants were randomly allocated in a 2:1 group allocation to discontinue or continue using APP. The research was conducted across seven European pediatric incontinence centers. The study included treatment-naïve children aged 4-8 years with severe (7/7 wet nights per week) mono-symptomatic NE, who had used nighttime protection for at least 6 months prior to the study. The study consisted of a 4-week run-in period (± 7 days), where all children slept wearing APP (DryNites®). At week 4 (± 7 days), if meeting randomization criteria (7/7 wet nights during the last week of run-in), participants were randomized to continue to sleep in APP or to discontinue their use for a further 4 weeks, with the option of another 4 weeks in the extension period. The primary outcome was the difference between groups of wet nights during the last week of intervention. Quality of life (QoL) and sleep were secondary endpoints. In total, 105 children (43 girls and 62 boys, mean age 5.6 years [SD 1.13]) were randomized (no-pants group n = 70, pants group n = 35). Fifteen children (21%) in the no-pants group discontinued early due to stress related to the intervention. Children in the no-pants group experienced fewer wet nights compared to the pants group during the last week (difference 2.3 nights, 95% CI 1.54-3.08; p < 0.0001). In the no-pants group, 20% responded to the intervention, of whom 13% had a full response. Clinical improvement was detected within 2 weeks. Sleep and QoL were reported as negatively affected by APP discontinuation in the extension period but not in the core period.    Conclusion: A ~ 10% complete resolution rate was associated with discontinuing APP. While statistically significant, the clinical relevance is debatable, and the intervention should be tried only if the family is motivated. Response was detectable within 2 weeks. Discontinuing APP for 4-8 weeks was reported to negatively affect QoL and sleep quality. No severe side effects were seen.Trial registration: Clinicaltrials.gov Identifier: NCT04620356; date registered: September 23, 2020. Registered under the name: "Effect of Use of DryNites Absorbent Pyjama Pants on the Rate of Spontaneous Resolution of Paediatric Nocturnal Enuresis (NE)."

A typical case of tick-borne encephalitis.

Tick-borne encephalitis is a rare infection in Denmark. The infection has been endemic to the island of Bornholm for many years. During the past 10 years, transmission has occurred in other parts of Denmark, particularly North Zealand. This case report describes a typical tick-borne encephalitis case diagnosed in the first viraemic phase of the disease course. Clinical presentation and diagnostic criteria are described.

The effect of methylphenidate for giggle incontinence in children.

INTRODUCTION: Giggle incontinence (GI) is a rare form of urinary incontinence that occurs during or immediately after laughing due to involuntary and complete bladder emptying. Few studies in the literature report that methylphenidate can be effective in treatment of this condition. OBJECTIVE: The aim of this study is to characterize children with GI and evaluate their response to methylphenidate, as well as describe treatment duration, dosage of methylphenidate, relapse rates after discontinuation of medication, and side effects. METHODS: Medical records and 48-h frequency-volume charts from children treated with methylphenidate for GI in the period January 2011-July 2021 were retrospectively analyzed. RESULTS: Eighteen children were diagnosed with GI and fulfilled inclusion criteria. Fifteen patients were included in analysis, as 3 out of 18 children decided not to take the methylphenidate that was prescribed. In total, 14 out of the 15 GI patients treated with methylphenidate experienced clinical effect. All patients included in the study had methylphenidate prescribed in a dose range of 5-20 mg daily. Treatment duration ranged from 30 to 1001 days, with a median of 152 days (IQR 114, 243.5). Ten children experienced complete response and two of those reported symptom relapse after discontinuation of the methylphenidate. Only mild and short-lasting side effects were reported by two patients. DISCUSSION: Our study demonstrates that methylphenidate is an effective treatment in children diagnosed with GI. Side effects are mild and uncommon.

[Tubulointerstitial nephritis and uveitis syndrome].

Tubulointerstitial nephritis and uveitis (TINU) syndrome in children is an uncommon, underreported condition. Onset of renal and ocular symptoms is often not simultaneous with nephritis which may precede uveitis by several months. A variable treatment response and a propensity for relapse characterize the syndrome. This is a case report of a previously healthy 14-year-old boy with TINU syndrome, emphasizing the need for long-term interdisciplinary treatment and monitoring. Also, the importance of repetitive screening of patients with uveitis for renal disease and ophthalmological evaluation of children with nephritis is emphasized.

Oral and Anal Carriage of Streptococcus pneumoniae Among Sexually Active Men With HIV Who Have Sex With Men.

People with HIV are at increased risk of pneumococcal disease. We investigate oral and anal carriage rates of Streptococcus pneumoniae by molecular methods among 82 men with HIV who have sex with men (MSM). A questionnaire, oral wash, and anal swab samples were obtained at baseline and 12 months. Oral carriage rates were 32.9% (27/82) at baseline and 41.7% (30/72) at follow-up. Anal carriage rates were 2.4% (2/82) at baseline and 2.9% (2/70) at follow-up. Genogroup 24 was predominant. Results suggest high oral carriage rates of S. pneumoniae among MSM living with HIV. A minority were anal carriers.

Transcutaneous electrical nerve stimulation as add-on therapy in children receiving anticholinergics and/or mirabegron for refractory daytime urinary incontinence: A retrospective cohort study.

AIMS: To investigate if children with daytime urinary incontinence (DUI) and overactive bladder (OAB) refractory to standard urotherapy and medicinal treatment, would experience improvement in symptoms after add-on treatment with transcutaneous electrical nerve stimulation (TENS). METHODS: Children were retrospectively enrolled from tertiary referral centers at Aarhus and Aalborg University Hospitals. All data were retrieved from the patients' journals. All children were prescribed TENS as an add-on treatment to the highest-tolerable dose of medicinal treatment in a standardized regime of 2 h a day for around 3 months. Primary endpoints were the number of wet days per week (WDPW) and incontinence episodes per day. Effect of treatment was defined as greater or equal to 50% reduction in the frequency of DUI episodes. Secondary endpoints were to establish predictive factors for the effect of treatment using logistic regression. RESULTS: Seventy-six children diagnosed with DUI and OAB refractory to treatment with standard urotherapy and pharmacological treatment, at the age of 5-16 years were included from February 2017 to February 2020. A reduction in WDPW (from 6.31 [5.86-6.61] to 4.27 [3.45-4.90], p < 0.05) and incontinence episodes per day (from 2.45 [1.98-2.91] to 1.43 [1.07-1.80], p < 0.05) was observed. Twelve patients became completely dry. At 6 months follow-up, seven of the 12 complete responders had relapsed while five remained dry. A history of constipation before TENS was a predictor of poor treatment response (p = 0.016). CONCLUSIONS: TENS as add-on to anticholinergic treatment seems effective in a number of children with treatment-refractory DUI.

Description of the voided urinary microbiota in asymptomatic prepubertal children - A pilot study.

BACKGROUND: Recently, it has been established that the urine of a healthy adult bladder contains a microbiota and that urinary dysbiosis may be involved in the development of urinary tract diseases. The urinary microbiota and its relation to bladder health and disease in children is yet to be established. The objective of the present study was to investigate the voided urinary microbiota in asymptomatic prepubertal children. STUDY DESIGN: Thirty asymptomatic children (15 boys and 15 girls) participated in the study. Bacterial DNA in "clean-catch" midstream urine (CC MSU) samples was analysed using Illumina MiSeq sequencing of the V4 region of the bacterial 16 S rRNA gene. All children had normal bladder function as ensured by uroflowmetry, ultrasonic post-void residual, and frequency-volume charts. Bladder-related parameters and gender comparisons were analysed statistically by parametric and non-parametric tests. Alpha diversity, beta diversity, and a Venn diagram were used to analyse sequencing data. RESULTS: All CC MSU samples contained bacterial DNA. The voided urinary microbiota differed significantly between girls and boys in terms of operational taxonomic unit (OTU) richness, Shannon diversity index, and relative abundances of bacterial genera, but not for evenness. The urine of girls was dominated by Prevotella (18.2%), Porphyromonas (12.9%), Ezakiella (8.1%), Prevotella 6 (7.4%), and Dialister (7.0%). Porphyromonas (22.4%) was the most abundant genus in boys, followed by Ezakiella (12.0%), Campylobacter (11.6%), Prevotella (8.6%), and Dialister (3.7%). Girls had 10 unique core OTUs, whereas boys had no unique core OTUs. Porphyromonas appeared as a shared core OTU between genders. DISCUSSION: Contrary to previous findings, this study found significant differences in the voided urinary bacterial composition among asymptomatic prepubertal children. Moreover, the bacterial composition diverged from that found among healthy adults by other research groups. Among adults, the gender specific urinary microbiota has been hypothesised to be caused by anatomical differences in the reproductive organs and differences in sex hormone levels. This could also be evident for asymptomatic prepubertal children as sex hormone levels are different even at the prepubertal stage. The limitations of the study encompass small sample size and urine collection by CC MSU with risk of contamination from surrounding areas. CONCLUSIONS: This study documents that CC MSU samples of asymptomatic prepubertal children are not sterile. The composition of the voided urinary microbiota seems gender specific and unequal to that of healthy adults. The role of the urinary microbiota in paediatric urological disorders should be considered in future studies.

Oral and anal carriage of Neisseria meningitidis among sexually active HIV-infected men who have sex with men in Denmark 2014-15.

INTRODUCTION: Outbreaks of invasive meningococcal disease (IMD) among men who have sex with men (MSM) caused by a hypervirulent, non-encapsulated Neisseria meningitidis (Nm) clone belonging to genogroup C have been described. We aimed to determine the oral and anal carriage rates and genogroups of Nm among MSM living with HIV. METHODS: Sexually active MSM living with HIV were included. A questionnaire, an oral wash sample and an anal swab were collected at baseline and 12 months follow-up. Identification of Nm and genogrouping was performed using real-time polymerase chain reaction analysis. RESULTS: Among 82 MSM, the Nm carriage rate was 31.7% (95% CI 21.9-42.9) at baseline. The oral carriage rate was 24.4% (95% CI 15.6-35.1) and the anal rate was 11.0% (95% CI 5.1-19.8). Non-groupable Nm were most prevalent followed by genogroup B and genogroup Y. Rates were similar at follow-up. CONCLUSION: Strains of Nm were detected in both oral washes and anal samples in our study. Our results suggest that Nm may be transmitted sexually among MSM. Non-groupable Nm were predominant in our population and no genogroup C Nm were detected.

COVID-19 reopening causes high risk of irritant contact dermatitis in children.

INTRODUCTION: Childhood irritant contact dermatitis (ICD) is the most common cause for developing chronic hand eczema as an adult. The COVID-19 reopening in Denmark included regulations introducing frequent hand washing. The aim of the present study was to evaluate if frequent hand washing increases the incidence of ICD in children. METHODS: We conducted an observational study in Denmark during the reopening of schools and daycare facilities for children aged 0-12 years (April 22nd to May 1st 2020). A questionnaire was sent out to parents in four municipalities consisting of 20 questions about frequency of hand washing, use of hand sanitiser, symptoms of ICD, atopic dermatitis, allergy and predispositions. RESULTS: The study included 6,273 children. In children without any prior symptoms of dermatitis, 42.4% experienced ICD (dry, red and itchy skin) due to increased hand hygiene. Schoolchildren had a 1.5 times greater relative risk of developing ICD than preschool children. Frequency of hand washing was a strong risk factor, whereas this was not the case for alcohol-based hand sanitiser. Hand washing 7-10 times/day and >10 times/day increased the relative risk by 1.83 and 2.23 times, respectively. CONCLUSIONS: A higher frequency of hand washing during the COVID-19 reopening increased the incidence of ICD in children. Hand hygiene is essential in our fight against novel coronavirus, but prophylactic initiatives are important to reduce the possible long-term consequences of ICD in children. FUNDING: none TRIAL REGISTRATION: Clinicaltrials.gov (NCT04375410).

[The endocrine and metabolic link between COVID-19, diabetes and obesity].

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome corona virus 2. High age, hypertension, diabetes, and obesity are risk factors for severe COVID-19 with increased mortality. In this review, we discuss potential mechanisms by which diabetes and obesity modulate the host viral interactions and host-immune response. Glucose levels should be monitored rigorously, and patient-tailored aggressive treatment of hyperglycaemia is recommended, often with the use of insulin. Persons with diabetes and obesity are susceptible to severe outcomes from COVID-19.

Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark - the SHADE.

BACKGROUND: Women living with HIV (WLWH) have high rates of persistent high-risk human papillomavirus (hrHPV) infections and cervical cancer. We aimed to assess the distribution of hrHPV genotypes, risk factors of type-specific hrHPV persistence, and high-grade squamous intraepithelial lesions or worse (≥HSIL) in WLWH in Denmark. METHODS: From the prospective Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) we identified WLWH with a positive hrHPV test during the study period; 2011-2014. HIV demographics were retrieved from the Danish HIV Cohort Study and pathology results from the The Danish Pathology Data Bank. Logistic regression was used to identify risk factors associated with persistent hrHPV infection (positivity of the same hrHPV type in two samples one-two years after the first hrHPV positive date) and ≥ HSIL. RESULTS: Of 71 WLWH, 31 (43.7%) had persistent hrHPV infection. Predominant hrHPV genotypes were HPV58, 52, 51, and 35 and most frequently observed persistent genotypes were HPV52, 33 and 31. CD4 < 350 cells/µL predicted genotype-specific hrHPV persistence (adjusted OR 4.36 (95%CI: 1.18-16.04)) and ≥ HSIL was predicted by prior AIDS (adjusted OR 8.55 (95% CI 1.21-60.28)). CONCLUSIONS: This prospective cohort study of well-treated WLWH in Denmark found a high rate of persistent hrHPV infections with predominantly non-16/18 hrHPV genotypes. CD4 count < 350 cells/µL predicted hrHPV persistence, while prior AIDS predicted ≥HSIL.

[Familial hypomagnesaemia with secondary hypocalcaemia as a cause of seizures in children].

This case report presents a three-month-old girl, previously healthy, who was admitted to the hospital due to a cyanotic episode during breastfeeding. The episode was initially interpreted as aspiration. She had recurrent generalised seizures, and blood tests revealed hypomagnesaemia and hypocalcaemia. The electrolyte abnormalities were corrected by intravenous magnesium with subsequent normalisation of the calcium level. Genetic testing discovered a deletion in the TRPM6, which is associated with familial hypomagne-s-aemia with secondary hypocalcaemia. It is important to identify electrolyte disturbances in infants with afebrile seizures.

Cardiac Microvascular Dysfunction in Women Living With HIV Is Associated With Cytomegalovirus Immunoglobulin G.

BACKGROUND: People living with HIV (PLWH) appear to be at increased risk of cardiovascular disease (CVD), and this is possibly more pronounced in women living with HIV (WLWH). In the general population, men are more likely to develop obstructive coronary artery disease (CAD), and women often present with a nonobstructive pattern with cardiac microvascular dysfunction. We investigated cardiac microvascular function in men and women living with HIV and tested for association with cytomegalovirus (CMV) immunoglobulin G (IgG), as this has been associated with CVD in PLWH. METHODS: In a cross-sectional study, 94 PLWH on antiretroviral therapy were scanned with 82Rb positron emission tomography/computed tomography at rest and during adenosine-induced stress, which enables the quantification of the myocardial flow reserve (MFR). CMV IgG was measured in plasma. RESULTS: WLWH had significantly lower MFR compared with men living with HIV (MLWH; P = .003), and >45% of the women had an MFR indicative of cardiac microvascular dysfunction, whereas this was only true for 24% of men (P = .03). CMV IgG concentrations were inversely associated with MFR among WLWH but not MLWH (P = .05 for interaction). CONCLUSIONS: In this first study comparing MFR in women and men living with HIV, we found that WLWH had significantly lower MFR than MLWH and 45% of the women had cardiac microvascular dysfunction despite younger age and lower cardiovascular risk. Furthermore, CMV IgG was inversely associated with MFR among women but not men. This calls for attention to CVD among young WLWH even with low cardiovascular risk.

[Antiretroviral HIV therapy and hormonal contraceptives].

HIV guidelines recommend assessment of conception issues for all people living with HIV. Studies have shown negligible risk of HIV transmission from well-treated patients with HIV, and therefore condoms are no longer recom-mended to reduce HIV transmission. Some antiretroviral agents are metabolised through the same enzyme systems in the liver as hormonal contraceptives, which can affect the plasma concentration of both drug classes and the effect of the drugs, including reduced contraceptive efficacy. This review discusses the interactions between antiretroviral agents and hormonal contraceptives.

Prevalence of cervical, oral, and anal human papillomavirus infection in women living with HIV in Denmark - The SHADE cohort study.

BACKGROUND: Women living with HIV (WLWH) have elevated risk of human papillomavirus (HPV) related cancers. OBJECTIVES: To assess prevalence, distribution and concordance of cervical, oral, and anal HPV infection, and predictors of oral and anal HPV in WLWH in Denmark. STUDY DESIGN: WLWH followed in the Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) were enrolled and examined for cervical, oral, and anal HPV infection. Logistic regression models were used to identify predictors of anal and oral HPV. RESULTS: A total of 214 of 334 WLWH had sufficient DNA for analysis at all three anatomical sites and were included in analyses. Cervical, oral, and anal high-risk (hr) HPV prevalence were 28.0%, 3.7% and 39.3%. Most frequent i) cervical, ii) oral and iii) anal hrHPV genotypes were i) hrHPV58 (8.4%), 52 (5.1%), 16 (5.1%) and 51 (5.1%); ii) 52 (1.4%) and iii) 51 (9.3%), 58 (8.9%), 16 (7.0%) and 18 (7.0%). Among present cervical, oral, and anal hrHPV genotypes, 6.7%, 12.5% and 17.9% were targeted by the 2-or 4-valent HPV vaccines, whereas 50.0%, 50.0% and 42.9% of hrHPV genotypes were covered by the 9-valent HPV vaccine. Anal HPV infection was predicted by cervical HPV infection (adjusted OR 4.47 (95%CI 2.25-8.89)). CONCLUSION: Cervical and anal HPV infection were highly prevalent in WLWH. Non-16/18 hrHPV genotypes were predominant at all anatomical sites. Almost half of all hrHPV infections at the three anatomical sites could have been prevented by childhood/adolescent vaccination with the 9-valent HPV vaccine.

Prevalence and significance of Mycoplasma genitalium in women living with HIV in Denmark.

OBJECTIVE: Mycoplasma genitalium (M. genitalium) is a sexually transmitted pathogen associated with urethritis, cervicitis, and pelvic inflammatory disease. Previous studies have shown a strong association between M. genitalium and HIV infection, therefore screening and treatment for M. genitalium has been suggested as part of HIV prevention strategies. The objective of this study was to determine the prevalence of M. genitalium in women living with HIV (WLWH) in Denmark, and to compare the result with data on symptoms from the lower abdomen, sexual habits and immune status. 234 women, recruited from Danish HIV centres as part of a larger observational study on aspects of living with HIV as a woman (the SHADE study), were included. RESULTS: We tested cervical samples for M. genitalium by specific PCR. We found three samples positive (1.3%). The women were between 30 and 50 years old, all were of Asian origin, sexually active, and on antiretroviral treatment with supressed HIV RNA and CD4 count >350 cells/µL. None reported symptoms from the lower abdomen. The prevalence of M. genitalium infection in WLWH in Denmark is low, thus systematic screening for M. genitalium in this group does not seem relevant.

[The significance of HIV to bone mineral density].

The life expectancy in well-treated HIV-infected persons approaches that of the general population, but HIV-infected persons have a greater incidence of fractures and osteoporosis. A decrease in bone mineral density is observed primarily during the first 1-2 years of antiretroviral therapy. Dual X-ray absorptiometry scan should be considered in HIV-infected men ≥ 50 years and postmenopausal women. In case of osteoporosis, bisphosphonate treatment should follow guidelines for the general population. Future research should focus on pathogenesis and prevention of bone density loss in HIV.