Hidradenitis Suppurativa : clinical studies with focus on evaluation

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of mainly unknown aetiology which in most cases involves axillae or groins and that can last for decades. In this thesis different clinical aspects of HS are studied: development of a clinical scoring system, relation to smoking and obesity, outcome of laser surgery, bacteraemia in HS patients and distribution of the neuroendocrine marker protein gene product (PGP) 9.5 in HS skin biopsies. In Paper I the objective is to evaluate the modified Hidradenitis Suppurativa Score (HSS) and to study the impact of BMI and smoking habits on disease severity. Altogether 246 HS patients completed the Dermatology Life Quality Index (DLQI) questionnaire and 115 were scored by HSS. Points were given for regions, types of lesion (nodules, fistulas), total area involved, and whether lesions were separated by normal skin. A positive correlation of fair degree between HSS and DLQI was found, as well as significant higher median scores in more advanced HS, in smokers compared to non smokers and in obese women compared to those of normal weight, respectively. The results indicate that the HSS reflects disease severity, and may be a relevant outcome measure in clinical trials. In Paper II scanner-assisted carbon dioxide laser treatment with subsequent healing by secondary intention is evaluated in 34 HS patients, with in total 67 operating sites. They were interviewed by telephone about recurrences and end results, after a mean follow-up time of 34.5 (range 7 87) months. Four patients had had recurrences in one of the treated areas. In twelve cases, lesions had developed separated from the initial surgical site by >5 cm. Twenty-five patients had flare-ups of HS lesions in another anatomical region. Eight had no symptoms of HS at all during the follow-up period. Mean healing time was 4 (range 3 5) weeks. The conclusion is that scanner-assisted carbon dioxide laser treatment of HS is an efficient treatment, well accepted by the patients. In Paper III the objective is to determine the number and type of bacteria circulating in the bloodstream in HS patients undergoing carbon dioxide laser surgery. Blood samples were taken before, during and after surgery in 21 patients with HS Hurley stage II, and from five healthy controls. Bacterial growth in the first blood sample was found in nine patients, from the second in ten and from the third in six. In one patient, bacteria were detected in all the three samples. The dominating bacteria were coagulase- negative staphylococci, of which most were subtyped as S. warneri. In six patients all samples were negative, which may indicate that the method of surgery itself caused no spread of bacteria. In Paper IV the presence and distribution of the nerve fibre-marker PGP 9.5 is investigated by immunohistochemistry. Biopsies were taken from the groin or axilla of 16 HS patients and 12 healthy controls. The median number of PGP 9.5 positive profiles was decreased in lesional epidermis, yet statistically significant only in the groin. A similar difference was found in lesional dermis of the axilla, whereas in the lesional upper dermis of the groin the median number of profiles was increased. Cells with strong PGP 9.5 immunofluorescence were few or absent in epidermis, but significantly increased in lesional dermal skin of the groin. It is possible that PGP 9.5 positive nerve fibres and cells have pathological roles in HS, but further investigations are needed

Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals.

OBJECTIVES: To determine the impact of pretreatment low-abundance HIV-1 drug-resistant variants (LA-DRVs) on virological failure (VF) among HIV-1/TB-co-infected individuals treated with NNRTI first-line ART. METHODS: We conducted a case-control study of 170 adults with HIV-1/TB co-infection. Cases had at least one viral load (VL) ≥1000 RNA copies/mL after ≥6 months on NNRTI-based ART, and controls had sustained VLs <1000 copies/mL. We sequenced plasma viruses by Sanger and MiSeq next-generation sequencing (NGS). We assessed drug resistance mutations (DRMs) using the Stanford drug resistance database, and analysed NGS data for DRMs at ≥20%, 10%, 5% and 2% thresholds. We assessed the effect of pretreatment drug resistance (PDR) on VF. RESULTS: We analysed sequences from 45 cases and 125 controls. Overall prevalence of PDR detected at a ≥20% threshold was 4.7% (8/170) and was higher in cases than in controls (8.9% versus 3.2%), P = 0.210. Participants with PDR at ≥20% had almost 4-fold higher odds of VF (adjusted OR 3.7, 95% CI 0.8-18.3) compared with those without, P = 0.104. PDR prevalence increased to 18.2% (31/170) when LA-DRVs at ≥2% were included. Participants with pretreatment LA-DRVs only had 1.6-fold higher odds of VF (adjusted OR 1.6, 95% CI 0.6-4.3) compared with those without, P = 0.398. CONCLUSIONS: Pretreatment DRMs and LA-DRVs increased the odds of developing VF on NNRTI-based ART, although without statistical significance. NGS increased detection of DRMs but provided no additional benefit in identifying participants at risk of VF at lower thresholds. More studies assessing mutation thresholds predictive of VF are required to inform use of NGS in treatment decisions

Screening and diagnosing depression in women visiting GPs' drop in clinic in Primary Health Care

<p>Abstract</p> <p>Background</p> <p>Only half of all depressions are diagnosed in Primary Health Care (PHC). Depression can remain undetected for a long time and entail high costs for care and low quality of life for the individuals. Drop in clinic is a common form of organizing health care; however the visits are short and focus on solving the most urgent problems. The aim of this study was to investigate the prevalence and severity of depression among women visiting the GPs' drop in clinic and to identify possible clues for depression among women.</p> <p>Methods</p> <p>The two-stage screening method with "high risk feedback" was used. Beck's Depression Inventory (BDI) was used to screen 155 women visiting two GPs' drop in clinic. Women who screened positive (BDI score ≥10) were invited by the GP to a repeat visit. Major depression (MDD) was diagnosed according to DSM-IV criteria and the severity was assessed with Montgomery-Asberg Depression Rating Scale (MADRS). Women with BDI score <10 constituted a control group. Demographic characteristics were obtained by questionnaire. Chart notations were examined with regard to symptoms mentioned at the index visit and were categorized as somatic or mental.</p> <p>Results</p> <p>The two-stage method worked well with a low rate of withdrawals in the second step, when the GP invited the women to a repeat visit. The prevalence of depression was 22.4% (95% CI 15.6–29.2). The severity was mild in 43%, moderate in 53% and severe in 3%. The depressed women mentioned mental symptoms significantly more often (69%) than the controls (15%) and were to a higher extent sick-listed for a longer period than 14 days. Nearly one third of the depressed women did not mention mental symptoms. The majority of the women who screened as false positive for depression had crisis reactions and needed further care from health professionals in PHC. Referrals to a psychiatrist were few and revealed often psychiatric co-morbidity.</p> <p>Conclusion</p> <p>The prevalence of previously undiagnosed depression among women visiting GPs' drop in clinic was high. Clues for depression were identified in the depressed women's symptom presentation; they often mention mental symptoms when they visit the GP for somatic reasons e.g. respiratory infections. We suggest that GPs do selective screening for depression when women mention mental symptoms and offer to schedule a repeat visit for follow-up rather than just recommending that the patient return if the mental symptoms do not disappear.</p

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Hidradenitis Suppurativa in Sweden : A Registry-Based Cross-Sectional Study of 13,538 Patients

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition with nodules and fistula formation and scarring. It is a debilitating disease with a severe negative impact on quality of life. There is a need for increased knowledge about the social and lifestyle characteristics of patients with HS in general, and pregnant women in particular. Objectives: The aims of this study were to investigate and describe social characteristics and comorbidity in all HS patients in Sweden as well as to study the prevalence of lifestyle factors associated with negative impact on health and pregnancy in Swedish pregnant women with HS. Methods: A registry-based cross-sectional study was performed by record linkage between Swedish registers covering the entire population. A cohort of 13,538 HS patients diagnosed with HS in specialised care during the years 2001-2014 and a subgroup of 1,368 HS patients who had undergone pregnancy during 2010-2015 were defined and described. Aggregated public data on the entire Swedish population and all pregnancies in 2014 were described for reference. Results: The HS population had an average age of 44 years on December 31, 2014. The prevalence of HS was 0.14%. In comparison to the Swedish reference population the HS patients were more often women, unmarried (36 vs. 44% married), and had lower education (68 vs. 82% with an upper-secondary school degree or higher) and lower income (39 vs. 16% made SEK <100,000 a year). Comorbidity was 3% for inflammatory bowel disease and 8% for type 2 diabetes. The subgroup analysis showed high prevalence of overweight, obesity, and smoking in pregnant women with HS. Conclusions: The results from this comprehensive characterisation of Swedish HS patients may be used to improve preventive measures, information, and care for this vulnerable group

Paxilline Prevents the Onset of Myotonic Stiffness in Pharmacologically Induced Myotonia: A Preclinical Investigation

Reduced Cl− conductance causes inhibited muscle relaxation after forceful voluntary contraction due to muscle membrane hyperexcitability. This represents the pathomechanism of myotonia congenita. Due to the prevailing data suggesting that an increased potassium level is a main contributor, we studied the effect of a modulator of a big conductance Ca2+- and voltage-activated K+ channels (BK) modulator on contraction and relaxation of slow- and high-twitch muscle specimen before and after the pharmacological induction of myotonia. Human and murine muscle specimens (wild-type and BK−/−) were exposed to anthracene-9-carboxylic acid (9-AC) to inhibit CLC-1 chloride channels and to induce myotonia in-vitro. Functional effects of BK-channel activation and blockade were investigated by exposing slow-twitch (soleus) and fast-twitch (extensor digitorum longus) murine muscle specimens or human musculus vastus lateralis to an activator (NS1608) and a blocker (Paxilline), respectively. Muscle-twitch force and relaxation times (T90/10) were monitored. Compared to wild type, fast-twitch muscle specimen of BK−/− mice resulted in a significantly decreased T90/10 in presence of 9-AC. Paxilline significantly shortened T90/10 of murine slow- and fast-twitch muscles as well as human vastus lateralis muscle. Moreover, twitch force was significantly reduced after application of Paxilline in myotonic muscle. NS1608 had opposite effects to Paxilline and aggravated the onset of myotonic activity by prolongation of T90/10. The currently used standard therapy for myotonia is, in some individuals, not very effective. This in vitro study demonstrated that a BK channel blocker lowers myotonic stiffness and thus highlights its potential therapeutic option in myotonia congenital (MC).</p

Development of a Clinical Scandinavian Registry for Hidradenitis Suppurativa; HISREG

Hidradenitis suppurativa (HS; or acne inversa) is a scarring and frequently persistent inflammatory disorder of the terminal hair follicles of apocrine gland-bearing skin in adults. Treatments include local or systemic antibiotics, hormones, retinoids and systemic immunosuppressive agents (1), although on evaluation these have been shown to have only limited or temporary effect. In refractory cases, surgery is necessary, and should be radical and performed as early as possible (2, 3). It is essential to establish a registry of HS in order to address the following important issues: to assess the safety and effectiveness of different treatments; to identify which specific patient subgroups have the best risk/benefit ratio for a given treatment; and to create benchmark data for quality assurance of the medical service. This manuscript presents the Scandinavian Registry for HS, HISREG

The continuum of personalized cardiovascular medicine: a position paper of the European Society of Cardiology

Kirchhof P, Sipido KR, Cowie MR, et al. The continuum of personalized cardiovascular medicine: a position paper of the European Society of Cardiology. European Heart Journal. 2014;35(46):3250-3257