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)."

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.

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.

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.

Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark.

BACKGROUND: Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV (WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. METHODS: WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load. RESULTS: Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. CONCLUSION: In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.

Prevalence and distribution of cervical high-risk human papillomavirus and cytological abnormalities in women living with HIV in Denmark - the SHADE.

BACKGROUND: Women living with HIV (WLWH) are at increased risk of persistent human papillomavirus (HPV) infection, cervical dysplasia and cervical cancer compared with women from the general population (WGP). We assessed the prevalence and distribution of cervical high-risk (hr) HPV infection and cytological abnormalities in WLWH compared with WGP in Denmark. Predictors of HPV and cytological abnormalities were estimated in WLWH. METHODS: WLWH consecutively enrolled in the Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) in 2011 and were examined for cervical HPV and cytological abnormalities. WLWH were matched on age and prior cytological findings with WGP from an earlier study. HIV demographics were retrieved from the nationwide Danish HIV Cohort Study. Logistic regression was used to estimate predictors of hrHPV and cytological abnormalities. RESULTS: Of 334 included WLWH 26.4 % were positive for hrHPV as opposed to 16.6 % WGP (p < 0.0001). WLWH had a higher number of multiple infections (>1 h genotype present) (38.5 % versus 25.7 %, p = 0.030). Hr genotypes in descending order of frequency were HPV58 (7.1 %), 52 (5.4 %), and 16 (4.8 %) in WLWH versus HPV16 (4.1 %), 52 (2.8 %) and 58 (2.4 %) in WGP. Predictors of hrHPV in WLWH were short duration of HAART (adjusted OR per year 0.90 (95 % CI 0.84-0.96)), AIDS prior to inclusion (adjusted OR 3.61 (95 % CI 1.75-7.46)), ≥5 lifetime sexual partners (adjusted OR 2.20 (95 % CI 1.08-4.49)), sexual debut <16 years of age (adjusted OR 2.05 (95 % CI 1.03-4.10)) and CD4 < 350 cells/µL (adjusted OR 2.53 (95 % CI 1.20-5.40)). Cytological abnormalities were prevalent in 10.4 % vs. 5.2 % (p = 0.0003) of WLWH and WGP. In WLWH with hrHPV, short duration of HAART predicted cervical dysplasia (adjusted OR per year 0.83 (95 % CI 0.71-0.97)). CONCLUSIONS: WLWH presented with more cervical hrHPV infections and cytological abnormalities, and a different distribution of hrHPV genotypes compared with WGP. Cervical hrHPV and cytological abnormalities were predicted by short duration of HAART.

Immune recovery in acute and chronic HIV infection and the impact of thymic stromal lymphopoietin.

BACKGROUND: Symptomatic primary HIV infection is associated with an adverse prognosis, and immediate initiation of combination antiretroviral therapy (cART) is recommended. However, little is known about immunological predictors of immune recovery. Thymic Stromal Lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cells homeostatic polyclonal proliferation and regulates Th17/regulatory T-cell balance, immunological functions known to be affected during primary HIV infection. The aim of this study was to describe immune recovery in primary and chronic HIV infection and possible impact of TSLP. METHODS: Prospective study including 100 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/µL, N = 42), late presenters without advanced disease (200-350 CD4+ T cells/µL, N = 24) and with advanced disease (<200 CD4+ T cells/µL, N = 20) and). Immune recovery was defined as increase in CD4+ T cells count from baseline to a given time of follow-up. Plasma TSLP was determined using ELISA and CD4+ T cell subpopulations (recent thymic emigrants, naïve and memory cells) were measured using flow cytometry at baseline and after 6, 12 and 24 months of cART. RESULTS: Immune recovery was comparable in all groups, and no differences in immune homeostasis were found between primary HIV infection and early presenters, whereas differences in absolute counts and proportions of CD4+ T cell subpopulations were found between primary HIV infection and late presenters. TSLP was elevated in primary HIV infection at baseline and after 24 months of cART. Interestingly, TSLP was negatively associated with proportion of recent thymic emigrants (correlation coefficient -0.60, p = 0.030). TSLP was not associated with immune recovery in primary HIV infection. CONCLUSIONS: Immune recovery was comparable in primary and chronic HIV infection whereas differences in absolute counts and proportions of CD4+ T cell subpopulations were found between primary HIV infection and late presenters supporting early initiation of cART. Higher plasma TSLP was found in primary HIV infection, and TSLP was associated with lower thymic output, but not with immune recovery. These findings indicate a possible role of TSLP in immune homeostasis in HIV infection but do not support TSLP to affect immune recovery in primary HIV infection.

Sexually transmitted infections and use of contraceptives in women living with HIV in Denmark - the SHADE cohort.

BACKGROUND: No Danish guidelines for screening of sexually transmitted infections (STIs) in women living with HIV (WLWH) exist, except for annual syphilis testing. Drug-drug interaction between hormonal contraceptives and some types of highly active antiretroviral therapy (HAART) occurs. We assessed prevalence of STIs, contraceptive choices and predictors of condom use in a cohort of WLWH in Denmark. METHODS: WLWH consecutively enrolled during their outpatient visits from 2011 to 2012. Gynaecological examination and an interview were performed at entry and 6-month follow-up. Inclusion criteria were HIV-1 infection and ≥ 18 years of age. Exclusion criteria were pregnancy, alcohol- or drug abuse impeding adherence to the protocol. At entry, participants were tested (and where appropriate, treated according to guidelines) for Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, and herpes simplex (HSV-1 and HSV-2). At follow-up, predictors of condom use were estimated in sexually active WLWH. RESULTS: In total, 334 of the 1,392 eligible WLWH in Denmark were included (median age and HIV duration: 42.5 and 11.3 years). Chlamydia trachomatis was present in four individuals (1 %), and six (2 %) tested positive for HSV-2 by PCR. None were positive for Neisseria gonorrhoeae, HSV-1 or had active syphilis. At follow-up, 252 (76 %) participated; 168 (70 %) were sexually active. Contraceptives were used by 124 (75 %); condoms were preferred (62 %). Having an HIV-negative partner predicted condom use (adjusted OR 3.89 (95 %CI 1.49-10.11)). In the group of participants of reproductive age without pregnancy desires 13 % used no birth-control. Possible drug-drug interaction between hormonal contraceptives and HAART was found in 13/14 WLWH receiving both kinds of medication. CONCLUSION: The prevalence of STIs in WLWH in Denmark was low. The need for annual STI screening is questionable. Condoms were preferred contraceptives, especially in WLWH with an HIV-negative partner. In this cohort, 13 % of WLWH of reproductive age were at risk of unintended pregnancies due to lack of birth-control. Finally, in the subgroup of WLWH receiving both hormonal contraceptives and HAART possible drug-drug interactions could occur.

Adherence to the cervical cancer screening program in women living with HIV in Denmark: comparison with the general population.

BACKGROUND: Women living with HIV (WLWH) are at increased risk of invasive cervical cancer (ICC). International HIV guidelines suggest cervical screening twice the first year after HIV diagnosis and thereafter annually. Adherence to the HIV cervical screening program in Denmark is unknown. METHODS: We studied women from a population-based, nationwide HIV cohort in Denmark and a cohort of age-matched females from the general population. Screening behaviour was assessed from 1999-2010. Adjusted odds ratios (OR's) for screening attendance in the two cohorts and potential predictors of attendance to guidelines were estimated. Pathology specimens were identified from The Danish Pathology Data Bank. RESULTS: We followed 1143 WLWH and 17,145 controls with no prior history of ICC for 9,509 and 157,362 person-years. The first year after HIV diagnosis 2.6% of WLWH obtained the recommended two cervical cytologies. During the different calendar intervals throughout the study period between 29-46% of WLWH followed the HIV cervical screening guidelines. Adjusted OR's of attendance to the general population screening program for WLWH aged 30, 40 and 50 years, compared to controls, were 0.69 (95% CI: 0.56-0.87), 0.67 (0.55-0.80) and 0.84 (0.61-1.15). Predictors of attendance to the HIV cervical screening program were a CD4 count > 350 cells/µL and HIV RNA < 500 copies/mL. Calendar period after 2002 and HIV RNA < 500 copies/mL predicted attendance to the general population cervical screening program. CONCLUSIONS: The majority of WLWH do not follow the HIV guidelines for cervical screening. We support the idea of cytology as part of an annual review and integration of HIV care and cervical screening in a single clinic setting.

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.

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.

Impact of gender on response to highly active antiretroviral therapy in HIV-1 infected patients: a nationwide population-based cohort study.

BACKGROUND: Impact of gender on time to initiation, response to and risk of modification of highly active antiretroviral therapy (HAART) in HIV-1 infected individuals is still controversial. METHODS: From a nationwide cohort of Danish HIV infected individuals we identified all heterosexually infected women (N=587) and heterosexually infected men (N=583) with no record of Hepatitis C infection diagnosed with HIV after 1 January 1997. Among these subjects, 473 women (81%) and 435 men (75%) initiated HAART from 1 January 1997 to 31 December 2009. We used Cox regression to calculate hazard ratio (HR) for time to initiation of HAART, Poisson regression to assess incidence rate ratios (IRR) of risk of treatment modification the first year, logistic regression to estimate differences in the proportion with an undetectable viral load, and linear regression to detect differences in CD4 count at year 1, 3 and 6 after start of HAART. RESULTS: At initiation of HAART, women were younger, predominantly of Black ethnicity and had a higher CD4 count (adjusted p=0.026) and lower viral load (adjusted p=0.0003). When repeating the analysis excluding pregnant women no difference was seen in CD4 counts (adjusted p=0.21). We observed no delay in time to initiation of HAART in women compared to men (HR 0.91, 95% CI 0.79-1.06). There were no gender differences in risk of treatment modification of the original HAART regimen during the first year of therapy for either toxicity (IRR 0.97 95% CI 0.66-1.44) or other/unknown reasons (IRR 1.18 95% CI 0.76-1.82). Finally, CD4 counts and the risk of having a detectable viral load at 1, 3 and 6 years did not differ between genders. CONCLUSIONS: In a setting with free access to healthcare and HAART, gender does neither affect time from eligibility to HAART, modification of therapy nor virological and immunological response to HAART. Differences observed between genders are mainly attributable to initiation of HAART in pregnant women.

Impact of gender on the risk of AIDS-defining illnesses and mortality in Danish HIV-1-infected patients: a nationwide cohort study.

BACKGROUND: Gender differences in the risk of AIDS-defining illness (ADI) and mortality have been reported in the HIV-1-infected (HIV-positive) population, with conflicting findings. We aimed to assess the impact of gender on the risk of ADI and death in HIV-positive patients infected sexually. METHODS: This was a population-based, nationwide cohort study of incident Danish HIV-positive individuals infected by sexual contact. Outcomes were progression to AIDS and death. We used Cox proportional hazards models and Poisson regression analyses to calculate the risk of progression to AIDS and mortality rate ratios (MRR) between risk groups and compared these with the general Danish population. RESULTS: We identified 587 heterosexually infected women, 583 men who have sex with women (MSW), and 1089 men who have sex with men (MSM). The total follow-up time was 13,708 person-y. At the time of HIV diagnosis MSM had a lower prevalence of AIDS compared to MSW. Women and MSW presented more often with tuberculosis and less often with AIDS-defining cancers compared to MSM. In the adjusted analyses we observed no differences in progression to AIDS. In the adjusted analyses of risk of death, there were no differences between the 3 risk groups, although we saw a trend towards a higher risk of death in older MSW. MSM had a lower risk of death compared to the background population than women and MSW. CONCLUSIONS: In the Danish HIV population, gender has no major impact on progression to AIDS or mortality. Differences in these factors between women, MSW, and MSM are mainly due to confounding from race and CD4 + cell count at diagnosis.

[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.

Adherence to national guidelines for initiation of antiretroviral regimens in HIV patients: a Danish nationwide study.

AIM: To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients. METHODS: We used a Danish nationwide cohort of HIV infected patients to calculate the fraction of patients who in the period 1997-2006 started HAART according to the guidelines from The Danish Society of Infectious Diseases. We used Kaplan-Meier tables to estimate time from fulfilling the criteria for start of HAART to initiation of the treatment. Cox regression and logistic regression was used to identify risk factors for delayed initiation of treatment and chance of being included in clinical trials. RESULTS: The study included 3223 patients, 74% of whom initiated HAART in the study period. Ninety-four% fulfilled the criteria for start of HAART, with minor differences over calendar periods. Ninety-four% initiated a recommended regimen or were included in a clinical trial. Intravenous drug use predicted initiation of a non-recommended regimen and delay in start of HAART, while non-Caucasians were less likely to be included in clinical trials. CONCLUSIONS: In a Western world setting, the adherence to national guidelines for start of HAART can be high. We suggest that simplicity of the guidelines, centralization of treatment and involvement of local clinicians in the development of guidelines are of major importance for high adherence to treatment guidelines.

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.

[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.