High-Affinity NIR-Fluorescent Inhibitors for Tumor Imaging via Carbonic Anhydrase IX.

Tumor imaging and delivery of therapeutic agents may be achieved by designing high-affinity and high-selectivity compounds recognizing a tumor cell-expressing biomarker, such as carbonic anhydrase IX (CA IX). The CAIX, overexpressed in many hypoxic solid tumors, helps adjust to the energy requirements of the hypoxic environment, reduces intracellular acidification, and participates in the metastatic invasion of adjacent tissues. Here, we designed a series of sulfonamide compounds bearing CAIX-recognizing, high-affinity, and high-selectivity groups conjugated via a PEG linker to near-infrared (NIR) fluorescent probes used in the clinic for optically guided cancer surgery. We determined compound affinities for CAIX and other 11 catalytically active CA isozymes by the thermal shift assay and showed that the affinity Kd value of CAIX was in the subnanomolar range, hundred to thousand-fold higher than those of other CA isozymes. Similar affinities were also observed for CAIX expressed on the cancer cell surface in live HeLa cell cultures, as determined by the competition assay. The NIR-fluorescent compounds showed excellent properties in visualizing CAIX-positive tumors but not CAIX-negative knockout tumors in a nude mice xenograft model. These compounds would therefore be helpful in optically guided cancer surgery and could potentially be developed for anticancer treatment by radiotherapy.

Aerobic vaginitis is associated with carbonic anhydrase IX in cervical intraepithelial neoplasia.

The aim of this study was to analyze the association between vaginal microbiota, carbonic anhydrase IX (CAIX) and histological findings of cervical intraepithelial neoplasia (CIN). The study included 132 females, among them 66 were diagnosed with high-grade intraepithelial lesion (CIN2, CIN3, and cancer), 14 with low-grade disease, and 52 assigned to the control group. An interview focused on the behavior risk factors, together with vaginal fluid pH measurement, wet mount microscopy, detection of Chlamydia trachomatis, and Trichomonas vaginalis were performed. After colposcopy, high-grade abnormalities were detected via direct biopsies and treated with conization procedure. Conuses were immuno-stained with CAIX antibody. The histological findings were CIN1 (n = 14), and CIN2+ (included CIN2 (n = 10), CIN3 (n = 49), and cancer (n = 7; squamous cell carcinomas)). Prevalence of bacterial vaginosis (BV) was similar between the groups. Moderate or severe aerobic vaginitis (msAV) was diagnosed more often among CIN2+ (53.0%) than CIN1 (21.4%). Moderate or strong immunostaining of CAIX (msCAIX) was not detected among CIN1 cases. Thus, msAV was prevalent in CAIX non-stained group (p = 0.049) among CIN2 patients. Co-location of msAV and msCAIX was found in CIN3. Regression model revealed that msAV associated with high-grade cervical intraepithelial neoplasia independently from smoking and the number of partners.

Experiences of childbirth care in Lithuania and Romania: Insights from the European Babies Born Better survey.

BACKGROUND: Data on experience and satisfaction of users are essential for improvement of health care, especially in the field of childbirth. The aim of this study was to compare childbirth care experiences in Lithuania and Romania. METHODS: Data derived from the EU Babies Born Better online survey were analyzed. Parturients from Lithuania (N = 373) and Romania (N = 359) who had given birth within the last 5 years were included. Participants were asked to (1) describe the best things in childbirth care and (2) suggest changes in the care received at their birthplace. Qualitative data were analyzed using a previously developed deductive coding framework. RESULTS: In agreement with previous findings from Austria, positive experiences mainly addressed care experienced at an individual level (in particular healthcare practitioners' competence and personality traits) and suggested changes mainly addressed services at birthplace (issues related to infrastructure, information and counseling, and empowerment). Responses not initially included in the coding framework addressed aspects such as informal payment (in both countries), desire for home birth (particularly in Lithuania), or mistreatment of parturients (particularly in Romania). CONCLUSIONS: We conclude that similar trends in childbirth care exist in Lithuania and Romania with regard to parturients' personal experiences and psychosocial needs and that addressing the needs of parturients is important for improving service provision.

'To be Informed and Involved': Women's insights on optimising childbirth care in Lithuania.

INTRODUCTION: The user expectations and experiences of healthcare services are acknowledged as components of the quality of healthcare evaluations. The aim of the study is to analyse women's experiences and views on childbirth care in Lithuania. METHODS: The study used the Babies Born Better (B3) online survey as the data collection instrument. The B3 is an ongoing longitudinal international project, examining the experiences of intrapartum care and developed as part of EU-funded COST Actions (IS0907 and IS1405). Responses to open-ended questions about (1) the best things about the care and (2) things in childbirth care worth changing are included in the current analysis. The participants are 373 women who had given birth within 5 years in Lithuania. A deductive coding framework established by the literature review was used to analyse the qualitative data. The framework involves three main categories: (1) the service, (2) the emotional experience and (3) the individually experienced care, each further divided into subcategories. RESULTS: Reflecting the experience and views regarding the service at birthplace women wished empowerment, support for their autonomy and to be actively involved in decisions, the need for privacy, information and counselling, especially about breastfeeding. In terms of emotional experience, women highlighted the importance of comprehensibility/feeling of safety, positive manageability of various situations and possibilities for bonding with the newborn. Individually experienced care was described by feedback on specific characteristics of care providers, such as competence, personality traits, time/availability and encouragement of esteem in women in childbirth. The possibilities of homebirth were also discussed. The findings reflected salutogenic principles. KEY CONCLUSIONS: The findings suggest that the Lithuanian healthcare system is in a transition from paternalistic attitude-based practices to a shift towards patient-oriented care. Implementation of the improvements suggested for women in childbirth care in Lithuania would require some additional services, improved emotional and intrapersonal aspects of care and a more active role for women. PATIENT/PUBLIC CONTRIBUTION: Patients and the public contributed to this study by spreading information about surveys and research findings through their involvement in service user groups that have an interest in maternity care. Members of the patients' groups and the public were involved in the discussion of the results.

Factors, associated with elevated concentration of soluble carbonic anhydrase IX in plasma of women with cervical dysplasia.

Precancerous lesions of human cervix uteri have a tendency for regression or progression. In cervical intraepithelial neoplasia grade 2 (CINII) case there is an uncertainty if a lesion will progress or regress. The carbonic anhydrase IX (CAIX) enzyme is overexpressed in cervical cancer which is more sensitive to radiotherapy. CAIX is associated with poor prognosis in solid hypoxic tumors. The aim of this study was to determine factors related to elevated soluble CAIX (s-CAIX) in high-grade intraepithelial lesion (HSIL) cases. METHODS: Patients diagnosed with HSIL (N = 77) were included into the research group whereas without HSIL (N = 72)-the control group. Concentration of the soluble CAIX (s-CAIX) in plasma was determined by the DIANA ligand-antibody-based method. C. trachomatis was detected from cervical samples by PCR. Primary outcomes were risk factors elevating s-CAIX level in HSIL group. Non-parametric statistical analysis methods were used to calculate correlations. RESULTS: The s-CAIX level in patients with HSIL was elevated among older participants (rs = 0.27, p = 0.04) and with C. trachomatis infection (p = 0.028). Among heavy smokers with HSIL, the concentration of s-CAIX was higher in older women (rs = 0.52, p = 0.005), but was not related to the age of heavy smokers' controls (τ = 0.18 p = 0.40). CONCLUSION: The concentration of s-CAIX was higher among older, heavy smoking and diagnosed with C. trachomatis patients. All these factors increased the risk for HSIL progression.

Chikungunya associated vulvitis: case report and literature review / Vulvite associada a Chikungunya: relato de caso e revisão de literatura

Introduction: Chikungunya virus is spreading worldwide due to migration and globalization and could be presented with systemic and with unusual symptoms. Objective: To report a case of virus-transmitted infection detected in a woman during the gynecological examination at a vulvar clinic. Case report: A 73-year-old Caucasian woman attended a vulvar clinic because of dyspareunia and vulvar burning. Ulcers were observed on labia minora and perineum. A Chikungunya was diagnosed by seroconversion in paired specimens. She was prescribed prednisolone 40 mg once a day for 10 days. After oral steroid treatment, the woman had no body rashes or lesions on her genitals. Conclusion: This study emphasized that rare signs of unusual vulvitis with ulcers could be associated with Chikungunya infection.

Introdução: O vírus Chikungunya está se espalhando pelo mundo por conta da migração e da globalização, podendo apresentar sintomas sistêmicos e incomuns. Objetivo: Relatar um caso de infecção pelo vírus detectado em uma mulher por ocasião do exame ginecológico em clínica de patologia vulvar. Relato do caso: Uma mulher caucasiana de 73 anos foi a uma clínica vulvar por causa de dispareunia e queimação vulvar. Úlceras foram observadas nos pequenos lábios e no períneo. O diagnóstico de Chikungunya foi realizado por soroconversão em espécimes pareados. Foi prescrita prednisolona 40 mg uma vez ao dia por dez dias. Após o tratamento com esteróides orais, a mulher não apresentou erupções ou lesões nos órgãos genitais. Conclusão: Este estudo enfatizou que quadros raros de vulvite com úlcera podem estar associados à infecção por Chikungunya.

Evaluation of Chlamydia trachomatis and HR-HPV infection in women living with HIV: a cross-sectional study / Avaliação da infecção por Chlamydia trachomatis e HR-HPV em mulheres vivendo com HIV: um estudo transversal

Introduction: Infections caused by Chlamydia trachomatis (CT) and Human Papilloma Virus (HPV) are among the most prevalent sexually transmitted infections (STIs) worldwide. CT infection in women living with the human immunodeficiency virus (HIV) can facilitate HIV transmission by increasing HIV shedding in cervicovaginal secretions. The prevalence of Human papillomavirus (HPV) infection is higher in women living with HIV when compared to HIVnegative women, even when comparing those with the same sociodemographic characteristics. Generally, they have a high viral load and a higher persistence of viral infection, which increases the risk of developing premalignant and malignant lesions in the lower genital tract. Objective: To evaluate the frequency of CT and High-Risk HPV (HR-HPV) infection among women living with HIV and the association with sociodemographic, behavioral and clinical characteristics. Methods: Cross-sectional study carried out with a population of 66 non-pregnant women aged between 18 and 70 years living with HIV and/or acquired immunodeficiency syndrome (AIDS) at the Hospital Universitário Antônio Pedro, Universidade Federal Fluminense (UFF), Niterói (RJ), Brazil, between the period of March 1, 2018 and October 31, 2018. A standardized questionnaire was applied including sociodemographic and behavioral characteristics, and clinical information (use of oral contraceptives, Antiretroviral Therapy (ART), cluster of differentiation 4 (CD4) cell count, and viral load). Endocervical samples were collected for CT (COBAS 4800® system, Roche) and HPV (COBAS® HPV test, Roche) detection. Fisher's Exact Test was used to assess the association between variables. Regression analyses were performed using the logistic model in order to identify the factors associated with the outcomes of interest. Results: A frequency of 1.5% for CT and 21.2% for HR-HPV was found. Age was the single factor that presented statistical significance associated with HR-HPV infection. Conclusion: Our study showed that some women living with HIV promote risky behavior which could facilitate the acquisition of other STIs, such as HPV and CT infection. Some of them, with detected viral load, were not using condoms even with HIV-negative partners. These results may suggest that in addition to treatment and follow-up of women living with HIV, STIs counseling and guidance may play an important role in the control of STIs in this population

Introdução: As infecções causadas por Chlamydia trachomatis e por papilomavírus humano (HPV) estão entre as infecções sexualmente transmissíveis (IST) mais prevalentes em todo o mundo. A infecção por Chlamydia trachomatis em mulheres que vivem com HIV pode facilitar a transmissão do HIV, aumentando a disseminação do HIV cérvico-vaginal. A prevalência da infecção pelo HPV é maior em mulheres vivendo com HIV quando comparadas às mulheres HIV negativas, mesmo quando comparadas àquelas com as mesmas características sociodemográficas. Geralmente apresentam carga viral elevada e maior persistência de infecção viral, o que aumenta o risco de desenvolver lesões pré-malignas e malignas no trato genital inferior. Objetivo: Avaliar a frequência de infecção por Chlamydia trachomatis e HPV de alto risco (HR-HPV) em mulheres vivendo com HIV e sua associação com características sociodemográficas, comportamentais e clínicas. Métodos: Estudo transversal realizado com uma população de 66 mulheres não gestantes de 18 a 70 anos vivendo com HIV e/ou AIDS no Hospital Universitário Antônio Pedro, Universidade Federal Fluminense ­ Niterói (RJ), Brasil, entre 1º de março e 31 de outubro de 2018. Aplicou-se um questionário padronizado incluindo características sociodemográficas e comportamentais e informações clínicas (uso de anticoncepcionais orais, terapia antirretroviral, contagem de células CD4 e carga viral). Amostras endocervicais foram coletadas para detectar Chlamydia trachomatis (COBAS 4800® Roche) e HPV (COBAS ® HPV Roche). O teste exato de Fisher avaliou a associação entre as variáveis. As análises de regressão foram realizadas por meio do modelo logístico, a fim de identificar os fatores associados aos desfechos de interesse. Resultados: Encontrou-se frequência de 1,5% para Chlamydia trachomatis e 21,2% para HR-HPV. A idade foi o único fator que apresentou significância estatística associada à infecção por HR-HPV. Conclusão: Nosso estudo mostra que algumas mulheres vivendo com HIV praticam comportamentos de risco que podem facilitar a aquisição de outras IST, como a infecção por HPV e Chlamydia trachomatis. Algumas delas com carga viral detectada não usavam preservativo, mesmo com parceiros HIV negativos. Esses resultados podem sugerir que, além do tratamento e acompanhamento de mulheres vivendo com HIV, o aconselhamento e a orientação para IST podem desempenhar um papel importante no controle das IST nessa população.

ISIDOG Consensus Guidelines on COVID-19 Vaccination for Women before, during and after Pregnancy.

INTRODUCTION: Sars-CoV-2 infection poses particular problems in pregnancy, as the infection more frequently causes severe complications than in unaffected pregnant women or nonpregnant women with SARS-CoV-2 infection. Now that vaccination is available and rapidly being implemented worldwide, the question arises whether pregnant women should be vaccinated, and if so, whether they should receive priority. METHODS: Available scientific data and available guidelines about vaccination against SARS-CoV-2 were collected by the Guideline Committee of the International Society of Infectious Diseases in Obstetrics and Gynecology (ISIDOG) and were analyzed, discussed and summarized as guidelines for healthcare workers caring for pregnant women. Concluding statements were graded according to the Oxford evidence-based medicine grading system. RESULTS: There is evidence to consider pregnancy as a risk factor for serious complications of COVID-19 infection, even in the absence of additional risk factors, such as hypertension, diabetes and obesity which increase these risks even more in pregnancy. Currently available data slightly favor mRNA-based vaccines above vector-based vaccines during pregnancy and breastfeeding, until more safety data become available. CONCLUSION: ISIDOG advises policy makers and societies to prioritize pregnant women to receive vaccination against SARS-CoV-2 and favor the mRNA vaccines until further safety information becomes available.

The International Society for the Study of Vulvovaginal Disease Vaginal Wet Mount Microscopy Guidelines: How to Perform, Applications, and Interpretation.

OBJECTIVES: The aims of the study were to assess the available literature concerning the indications, performance, technique, and classification of wet mount microscopy (WMM) and to establish evidence-based recommendations. METHODS: Literature review from the main scientific databases was performed by the ad hoc "Vaginitis and Microbiome Committee" of the International Society for the Study of Vulvovaginal Disease. The document was approved by the executive council and membership of the International Society for the Study of Vulvovaginal Disease. RESULTS: Available data are limited and usually of low level of evidence. Nevertheless, it shows that WMM is capable of reducing misdiagnosis, overtreatment, and undertreatment of vaginal conditions. It has an excellent performance for the diagnosis of bacterial vaginosis and variable performance for trichomoniasis and candidiasis. It is the gold standard for aerobic vaginitis/desquamative inflammatory vaginitis. Currently, there is no recommendation to use WMM in the screening of asymptomatic women.The use of phase contrast is recommended to improve performance and reproducibility. Sampling location, devices, and technique have an impact on the results.Available scoring and classification scores have significant limitations. CONCLUSIONS: Wet mount microscopy is a point-of-care, inexpensive, and fast technique that, with practice, can be mastered by office clinicians. It should be considered a basic skill in the curricula of gynecology and obstetrics residencies. Recommendations are provided on sampling, reading, and scoring.

Vaginal pH and microbiota during fluconazole maintenance treatment for recurrent vulvovaginal candidosis (RVVC).

BACKGROUND: It is commonly stated that Candida in the vagina prefers a low pH to develop infection. However, mixed infections of Candida with bacterial vaginosis (BV) and aerobic vaginitis (AV) are rather common and may challenge the rule that Candida should only be looked for in low vaginal pH settings. In this study we tested whether the vaginal pH in acute vaginal candidosis is lower than in women successfully treated to prevent Candida recurrences. METHODS: Vaginal pH and microscopy findings of vaginal microbiota were recorded during 12 visits over 1.5 years in 117 patients medically monitored during a degressive fluconazole maintenance regimen for proven recurrent vulvovaginal candidosis (ReCiDiF trial). The fluctuation of the mean pH of and microscopic findings of the vaginal smears were studied before, during and after the treatment. RESULTS: The mean vaginal pH of women with acute infection before or after ending maintenance treatment was (4.7±0.8 and 4.8 ±1.0, respectively, p>0.05). During maintenance treatment with fluconazole, the pH dropped significantly to 4.5±0.8 (p=0.01). Depression of Lactobacilli spp. (increased lactobacillary grades) was more frequent during the acute, pre-treatment period (30.0%) than during the treatment period (23.1%, p=0.03). Aerobic vaginitis type flora was also more prevalent pre-treatment than during treatment (30.0% vs 22.2%, OR=0.7 (95%CI 0.5-0.9), p=0.01). DISCUSSION: In women with RVVC, acute vaginal Candida infection is associated with an increased pH, and disturbed vaginal bacterial microbiota. During fluconazole maintenance treatment, the pH drops to normal levels and the lactobacillary grade improves. CONDENSATION: Acute Candida vulvovaginitis can be associated with a disturbance of the vaginal microbiota. In patients with recurrent vulvovaginal candidosis, decrease of pH, and increase of Lactobacilli spp. were observed during fluconazole maintenance treatment. This pH drop was seen in all response groups. This contradicts the common belief that active vaginal Candida infection is related to low pH.

Pharmacotherapy for the treatment of vaginal atrophy.

INTRODUCTION: Despite its frequency, recognition and therapy of vulvovaginal atrophy (VVA) remain suboptimal. Wet mount microscopy, or vaginal pH as a proxy, allows VVA diagnosis in menopause, but also in young contraception users, after breast cancer, or postpartum. Intravaginal low dose estrogen product is the main therapy. Ultra-low-dose vaginal estriol is safe and sufficient in most cases, even in breast cancer patients, while hyaluronic acid can help women who cannot or do not want to use hormones. AREAS COVERED: The authors provide an overview of the current pharmaceutical treatment for vulvovaginal atrophy and provide their expert opinions on its future treatment. EXPERT OPINION: The basis of good treatment is a correct and complete diagnosis, using a microscope to study the maturity index of the vaginal fluid. Minimal dose of estriol intravaginally with or without lactobacilli is elegant, cheap and can safely be used after breast cancer and history of thromboembolic disease. Laser therapy requires validation and safety data, as is can potentially cause vaginal fibrosis and stenosis, and safer and cheaper alternatives are available.

Is multiple-site colonization with Candida spp. related to inadequate response to individualized fluconazole maintenance therapy in women with recurrent Candida vulvovaginitis?

OBJECTIVE: Although most women on fluconazole maintenance therapy for recurrent vulvovaginal candidosis experience a substantial improvement in quality of life, some do not respond to therapy. Is candidal colonization of extragenital sites related to suboptimal response to maintenance therapy? PATIENTS AND METHODS: Women included in a multicenter follow-up study (ReCiDiF) were evaluated for clinical signs and presence of yeasts in nose, mouth, anus, perineum, and urine. Candida was diagnosed by positive microscopy, confirmed by positive culture or polymerase chain reaction. After treatment, women were divided into groups according to their response to a fluconazole maintenance regimen (optimal, suboptimal, and nonresponders). RESULTS: The most frequent extravaginal Candida spp. were detected in urine (79.5%), perineum (78.6%), and anus (56.4%). Carriers of Candida in the mouth were more likely to have it in the anus (OR 3.2; 95% CI 1.4-7.7). Colonization in anus (OR 3.3; 95% CI 1.3-8.1) or in multiple extravaginal sites (OR 3.0; CI95% 1.2-7.4) was related to nonresponse to therapy. Candidal carriage in the anus did not increase anal and perianal symptoms. CONCLUSION: Women with anal carriage and multiple-site candidal colonization are less likely to respond to individualized decreasing dose fluconazole therapy.

Sexual behaviour and extra-genital colonisation in women treated for recurrent Candida vulvo-vaginitis.

OBJECTIVE: This study analyses a relation between sexual habits and the presence of Candida in extra-genital locations as well as a potential effect on therapy response. MATERIAL AND METHODS: Candida cultures were obtained from mouth, nose, anus, urine and perineum of 117 women enrolled in a RVVC treatment trial (ReCiDiF). Sexual behaviour and carriage rates of extra-genital Candida of women responding well to treatment were compared to that of non-responders. RESULTS: Most respondents were heterosexual. All but one practiced vaginal sex. Regular receptive oral sex was not related to multiple site colonisation with Candida (OR = 1.27; CI95% 0.36-4.48), nor to non-response to therapy (OR = 1.3; CI 95% 0.41-4.73). Also, masturbation was not related to response to therapy (OR 0.8; CI95% 0.31-1.84), nor was anal sex (OR = 0.54; CI95% 0.11-2.72). CONCLUSION: Neither oral nor casual anal sex, nor masturbation can be held responsible for the association of the multiple site/anal colonisation with Candida and inferior response to fluconazole maintenance therapy. Changing sexual behaviour during fluconazole maintenance treatment for RVVC in otherwise healthy women should not be advocated. Also, treatment of asymptomatic sexual partners of women with RVVC is not recommended.

Is non-response to fluconazole maintenance therapy for recurrent Candida vaginitis related to sensitization to atopic reactions?

PROBLEM: Is sensitization to atopic reaction related to treatment response of recurrent Candida vulvovaginal (RVVC)? METHOD OF THE STUDY: Analysis of ReCiDiF trial data of optimal (OR) and non-responders (NR) to fluconazole maintenance treatment, to explore medical history, physical status, family history, and vaginal immune response for potential sensitization to atopic reaction. RESULTS: Sociodemographic characteristics of 33 NR women were not different from 38 OR. NR had received higher number of different treatments (mean difference 1.6 different treatments (95% CI: 0.20-2.97), P = .03) and had more episodes of disease (P < .05). Multivariate regression analysis showed that family history of atopy (OR: 4.9, CI 95%: 1.1-22.2), duration of symptoms (OR: 1.2, CI 95%: 1.02-1.5), and vulvar excoriation (OR: 3.6, CI 95%: 1.4-9.3) were related to non-response. Vulvar excoriation at entry was the only statistically significant predictive factor for non-response in multivariate analysis with specificity 77.8% and sensitivity 51.6%. CONCLUSION: Women with RVVC with vulvar excoriation, longer duration of disease, and family history of atopic disease are at increased risk not to respond to maintenance fluconazole treatment.

Genital Tract Infections in an Isolated Community: 100 Women of the Príncipe Island.

Objective: To characterize the vaginal microbiome and the rate of sexually transmitted infections (STIs) in the women of Príncipe (São Tomé and Príncipe). Methods: Cross-sectional study of 100 consecutive women, invited for a free appointment and cervical cancer screening. A vaginal slide (wet mount microscopy) and a cervical sample (ThinPrep®) (Pap test, high risk human papillomavirus [HR-HPV], N. gonorrhea [NG], T. vaginalis [TV], and C. trachomatis [CT]) were obtained. Results: TV, NG, CT, and HIV were found in 8.0%, 2.0%, 3.0%, and 2.0%, respectively, and were more prevalent in younger women. HR-HPV was positive in 36.7%; 2 were positive for HPV18, but none for HPV16. Coinfection of HPV with other STIs was 8.3%. Prevalence of abnormal vaginal flora (AVF) was 82.5%, mostly bacterial vaginosis (BV) 54.6%, and moderate/severe aerobic vaginitis (msAV) 25.8%. HR-HPV was not related to BV (p = 0.67). The association of abnormal Pap test with msAV was not significant (p = 0.08). Conclusion: The prevalence of NG, CT, TV, and HR-HPV was according to expected, while that of HR-AVF was higher. The surprisingly low prevalence of HPV16 and HPV18 must be considered in the design of programs for prevention and vaccination; this setting can be useful as a model for postvaccination scenarios.

Provision of pharmaceutical care by community pharmacists across Europe: Is it developing and spreading?

RATIONALE, AIMS, AND OBJECTIVES: Pharmaceutical care involves patient-centred pharmacist activity to improve medicines management by patients. The implementation of this service in a comprehensive manner, however, requires considerable organisation and effort, and indeed, it is often not fully implemented in care settings. The main objective was to assess how pharmaceutical care provision within community pharmacy has evolved over time in Europe. METHOD: A cross-sectional questionnaire-based survey of community pharmacies, using a modified version of the Behavioural Pharmaceutical Care Scale (BPCS) was conducted in late 2012/early 2013 within 16 European countries and compared with an earlier assessment conducted in 2006. RESULTS: The provision of comprehensive pharmaceutical care has slightly improved in all European countries that participated in both editions of this survey (n = 8) with progress being made particularly in Denmark and Switzerland. Moreover, there was a wider country uptake, indicating spread of the concept. However, due to a number of limitations, the results should be interpreted with caution. Using combined data from participating countries, the provision of pharmaceutical care was positively correlated with the participation of the community pharmacists in patient-centred activities, routine use of pharmacy software with access to clinical data, participation in multidisciplinary team meetings, and having specialized education. CONCLUSIONS: The present study demonstrated a slight evolution in self-reported provision of pharmaceutical care by community pharmacists across Europe, as measured by the BPCS. The slow progress suggests a range of barriers, which are preventing pharmacists moving beyond traditional roles. Support from professional bodies and more patient-centred community pharmacy contracts, including remuneration for pharmaceutical care services, are likely to be required if quicker progress is to be made in the future.

Prevalence and distribution of Gardnerella vaginalis subgroups in women with and without bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is one of the leading causes of vaginal complaints among women of childbearing age. The role of Gardnerella vaginalis remains controversial due to its presence in healthy and BV-type vaginal microflora. The phenotypic and genotypic heterogeneity of G. vaginalis suggested the existence of strain variants linked with different health conditions. We sought to analyze prevalence and distribution of G. vaginalis subgroups (clades) in BV-positive (n = 29), partial BV (n = 27), and BV-negative (n = 53) vaginal samples from Lithuanian women. METHODS: Vaginal samples were characterized by Amsel criteria and the Nugent method. Bacterial signatures characteristic of BV and concomitant infections were identified by culture and PCR. Using singleplex PCR assays, G. vaginalis subgroups were identified in 109 noncultured vaginal specimens by targeting clade-specific genes. Isolated G. vaginalis clinical strains were subtyped and the presence of the sialidase coding gene was detected by PCR. Data analysis was performed using GraphPad Prism statistical software. RESULTS: G. vaginalis was found in 87% of women without BV. Clade 4 was most frequently detected (79.4%), followed by clade 1 (63.7%), clade 2 (42.2%), and clade 3 (15.7%). Multi-clade G. vaginalis communities showed a positive association with Nugent score (NS) ≥ 4 (OR 3.64; 95% CI 1.48-8.91; p = 0.005). Clade 1 and clade 2 were statistically significantly more common in samples with NS 7-10 (OR 4.69; 95% CI 1.38-15.88; p = 0.01 and OR 6.26; 95% CI 2.20-17.81; p ≤ 0.001, respectively). Clade 3 and clade 4 showed no association with high NS (OR 0.88; 95% CI 0.26-3.04; p = 1.00 and OR 1.31; 95% CI 0.39-4.41; p = 0.767, respectively). The gene coding for sialidase was detected in all isolates of clade 1 and clade 2, but not in clade 4 isolates. CONCLUSIONS: We showed an association between the microbial state of vaginal microflora and specific subgroups of G. vaginalis, the distribution of which may determine the clinical manifestation of BV. The frequent detection of clade 4 in the BV-negative samples might be due its lack of the gene coding for sialidase.

Aerobic vaginitis: no longer a stranger.

Aerobic vaginitis (AV) is the name given in 2002 to a vaginal infectious entity which was not recognized as such before. It is characterized by abnormal (dysbiotic) vaginal microflora containing aerobic, enteric bacteria, variable levels of vaginal inflammation and deficient epithelial maturation. Although AV and bacterial vaginosis (BV) share some characteristics, such as a diminished number or absence of lactobacilli, increased discharge (fishy smelling in BV, while in severe forms of AV, a foul, rather rotten smell may be present) and increased pH (often more pronounced in AV), there are also striking differences between the two. There is no inflammation in women with BV, whereas the vagina of women with AV often appears red and edematous, and may even display small erosions or ulcerations. The color of the discharge in BV is usually whitish or gray and of a watery consistency, whereas in AV it is yellow to green and rather thick and mucoid. Women with BV do not have dyspareunia, while some women with severe AV do. Finally, the microscopic appearance differs in various aspects, such as the presence of leucocytes and parabasal or immature epithelial cells in AV and the absence of the granular aspect of the microflora, typical of BV. Despite all these differences, the distinction between AV and BV was not recognized in many former studies, leading to incomplete and imprecise diagnostic workouts and erroneous management of patients in both clinical and research settings. The prevalence of AV ranges between 7 and 12%, and is therefore less prevalent than BV. Although still largely undiagnosed, many researchers and clinicians increasingly take it into account as a cause of symptomatic vaginitis. AV can co-occur with other entities, such as BV and candidiasis. It can be associated with dyspareunia, sexually transmitted infections (such as human papilloma virus, human immunodeficiency virus, Trichomonas vaginalis and Chlamydia trachomatis), chorioamnionitis, fetal infection, preterm birth and cervical dysplasia. Many other possible pathological associations are currently under investigation. The diagnosis of AV is made using wet mount microscopy, ideally using phase contrast. An AV score is calculated, according to: lactobacillary grade, presence of inflammation, proportion of toxic leucocytes, characteristics of the microflora and presence of immature epithelial cells. To circumvent the hurdle of microscopic investigation, some groups have begun to develop nucleic-acid-based and enzymatic diagnostic tests, but the detailed information obtained with phase contrast microscopy is irreplaceable. The best treatment is not yet fully determined, but it must be tailored according to the microscopic findings and the patient's needs. There is a role for local estrogen therapy, corticosteroids, antimicrobials and probiotics. Further research will reveal more precise data on diagnosis, pathogenesis, management and prevention.

Non-response to fluconazole maintenance treatment (ReCiDiF regimen) for recurrent vulvovaginal candidosis is not related to impaired glucose metabolism.

Is non-response to maintenance treatment for recurrent vulvovaginal candidosis (RCVV) related to the impaired glucose metabolism? In the ReCiDiF trial, women with RCVV were given a degressive regimen with fluconazole according to their clinical, microscopic and mycologic response. Data obtained from optimal, suboptimal and non-reponding patients were used for secondary analysis of medical history, physical status and family history for potential glucose impairment. Results were presented in means and percentages. Pearson chi-square, Fisher exact, Mann-Whitney U, Kruskal-Wallis and Spearman's correlation coefficient was calculated. P<.05 were interpreted as statistically significant. Sociodemographic characteristics and family and personal history of diabetes were not different between optimal, suboptimal and non-responders. The average HbA1c concentration was 5.1±0.3% in optimal, 5.0±0.4% in sub-optimal, and 5.1±0.3% in non-responding patients (P=1.0). There are no statistical differences between optimal, sub-optimal and non-respondents to treatment in all deciles of HbA1c among patients with recurrent candidosis (P=1.0). There was no difference among groups in fasting glucose concentration, nor after 30 min, 60 min or 120 min during the oral glucose tolerance test (OGTT) (P=.6). Area under the OGTT curve did not differ within groups (P=.8), nor was the deviation from the normal cut-off value any different (P=.8). Glucose concentration in vaginal rinsing fluid showed no correlation with responsiveness to treatment (P=.7). Glucose metabolism, BMI, personal or family history of diabetes are not related to non-response to maintenance treatment with fluconazole for patients with RVVC.