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Background and aims: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. Methods: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter-relationship determining overall survival. Results: MaVI prevalence was 11.1%, and median survival of these patients was 6.0months (95% CI, 5.1-7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4months in those with PS>1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1months in patients with PS 0-1, no ascites and Vp1-Vp2 MaVI (treated with surgery in 19.1% of cases). Conclusions: MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions.

Background and Aim: Data on the clinical pharmacokinetics of cannabidiol (CBD) are scanty. We explored the effect of demographic and clinical variables on plasma concentrations of purified CBD in patients with Dravet (DS) and Lennox–Gastaut syndrome (LGS).Methods: The study design was an open, prospective, multicenter expanded access program (EAP). Venous blood samples were drawn from patients between 8 and 9 am, before the CBD morning dose, 12 h apart from the last evening dose, and then 2.5 h after their usual morning dose.Results: We collected 127 plasma samples (67-morning pre-dosing and 60 post-dosing) from 43 patients (24 females, 19 males), 27 with LGS and 16 with DS. Mean ± standard deviation age was 26 ± 15 years. Duration of CBD treatment averaged 4.2 ± 2.9 months at 13.2 ± 4.6 mg/kg/day. CBD median trough plasma concentration was 91 ng/ml; it doubled to 190 ng/ml 2.5 h post-dosing (p < 0.001). Cannabidiol trough plasma concentrations were linearly related to daily doses (r = 0.564, p < 0.001). Median trough CBD plasma concentration-to-weight-adjusted dose ratio (C/D) was 32% higher (p < 0.02) in plasma samples from subjects aged 18 and over than in those under 18. Sex and concomitant antiseizure medications (ASMs) were not associated with significant variations in CBD C/D, but caution is required due to the potential influence of confounders.Conclusion: These are the first data on CBD pharmacokinetics in children and adults with LGS or DS in a real-world setting. The most relevant finding was the higher CBD C/D in adults. In practice, reduced weight-normalized doses might be required with aging to achieve the same CBD plasma levels.

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p&nbsp

Introduction. Although ART has improved the outcome of people living with HIV/AIDS, still some patients develop TB while receiving ART. The literature on the magnitude of this problem is still scarce in our setting especially northwestern Tanzania. This study was designed to determine the prevalence of active TB among HIV patients on ART and assess its potential risk factors.Methods. A retrospective cohort study was done among adult HIV-positive patients initiated on ART at Bugando Medical Centre. Patients who were TB positive before ART initiation were excluded. Data regarding demographic, clinical, and laboratory information, TB status on receipt of ART, and time on ART were collected and analyzed using STATA 11 to determine the prevalence of TB and its associated factors.Results. In total, 391 patients were enrolled in this study. The median age was 39 (32–46) years, and a total of 129 (32.99%) participants had CD4 counts µl and 179 (45.78%) had WHO stage 3 and 4 illnesses. A total of 43 (11.0%) participants developed TB while receiving ART which was independently associated with male gender (OR = 2.9;p=0.007), WHO clinical stage 3 and 4 (OR = 1.4;p=0.029), baseline CD4 count µl (OR = 9.1;p<0.001), and having not used IPT (OR = 3.1;p=0.05).Conclusions. Active TB is prevalent among HIV patients while receiving ART in northwestern Tanzania which is independently associated with male gender, advanced HIV disease, and nonuse of IPT. Universal HIV testing could reduce late HIV diagnosis and hence reduce the risk of developing TB while receiving ART in our setting. Also IPT should be widely used for those who are negative for TB on screening.

Background. The World Health Organization (WHO) recommends that children should be informed of their HIV status at ages 6 to 12 years and full disclosure of HIV and AIDS be offered in a caring and supportive manner at about 8 to 10 years. The objective of this study was to determine factors associated with HIV status disclosure and its effect on treatment adherence and health-related quality of life among children between 6 and 17 years of age living with HIV/AIDS in the Southern Highlands Zone, Tanzania, 2017. Methods. A hospital based unmatched case control study was conducted between April and September 2017. A total of 309 children between 6 and 17 years on ART for at least six months were enrolled in this study. Simple random sampling was employed in selecting the children from existing treatment registers. Data were collected using a structured questionnaire which included the WHO Quality of Life standard tool (WHOQOL-BREF 2012 tool) and treatment adherence manual. Multiple logistic regression was used to test for the independent effect of HIV status disclosure on treatment adherence and quality of life at p value less than 0.05. Results. Out of 309 children, only 102 (33%) had their HIV status disclosed to them. The mean age at HIV status disclosure was 12.39 (SD=3.015). HIV status disclosure was high among girls (51%), children aged 10-13 years (48.3%), and those living with their biological parents (59.8%). After adjusting for confounders, being aged between 10-13 and 14-17 years was associated with HIV status disclosure (AOR 19.178, p Conclusions. HIV status disclosure significantly improved adherence to treatment and quality of life among children living with HIV/AIDS.

Background: Prostatic carcinoma carries a high morbidity and mortality if it is not diagnosed early. In resource limited countries, patients are at increased risk of being diagnosed late as they are operated for presumed benign prostatic hyperplasia. The information on the magnitude and risk factors of this problem in our setting could assist in the overall optimization of care of patients at risk. Methods: A retrospective study of patients who underwent prostatectomy for presumed benign prostatic enlargement was done at Bugando University Hspital in Tanzania. Patients’ age, creatinine levels, urological Ultrasound, prostate specific antigen and Biopsy results were analyzed using STATA 11. The prevalence of incidental prostatic cancer was calculated and logistic regression was done for factors associated with incidental prostatic cancer. Results: In total, 152 patients were included in this study. The median age was 69 (SD 9.4) years, 16 (10.53%,) and 49 (32.24%) participants had Hydronephrosis and elevated creatinine levels respectively. Eighty six (58.56%) patients had PSA >10 ng/mL and in total; 33 (21.71%) had incidental prostatic carcinoma. The incidental prostatic carcinoma was independently associated with age of 70- 80years (AOR=2.8, p = 0.013) and PSA levels >10ng/mL (AOR=3.2, p=0.014). Conclusions: The prevalence of incidental prostatic carcinoma is high among patients undergoing transurethral prostatectomy for presumed benign prostatic hyperplasia in Tanzania with increased risk at age of 70-80 years and among those with PSA >10ng/mL. A national awareness campaign coupled with focused screening of patients above 60 years could increase the detection rate of prostatic carcinoma and reduce the magnitude of incidental diagnosis of this disease. Keywords: Incidental prostatic carcinoma, PSA, Tertiary level hospital, Tanzania

BACKGROUND Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. OBJECTIVES We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. METHODS Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. β-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. RESULTS Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest β-glucocerebrosidase activity. CONCLUSIONS GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society.

IntroductionDespite the benefits of early antenatal care visits for early prevention, detection, and treatment of potential complications in pregnancy, a high level of provider adherence to first-visit antenatal care standards is needed. However, little information is available regarding provider adherence to antenatal care in Tanzania. This study was performed to assess provider adherence to first-visit antenatal care standards and to apply stratified analysis to identify associated factors in Tanzania.MethodsData from the 2014-2015 Tanzania Service Provision Assessment Survey were used in this study. Provider adherence to first-visit antenatal care standards was measured using 10 domains: client history; aspects of prior pregnancies; danger signs of the current pregnancy; physical examination; routine tests; HIV testing and counseling; maintaining a healthy pregnancy; iron/folate supplements; tetanus toxoid vaccination, and preparation for delivery. A composite score was then created in which the highest quantile (corresponding to ≥60.5%) considered to provider adhering to first-visit antenatal care standards. Initially, a series of unadjusted logistic regression analyses according to the type of facility and managing authority were performed separately at each level (i.e., facility, provider, and client). Thereafter, all variables with P < 0.2 were fitted into the respective stratified multivariable logistic regression analysis using a 5% significance level.ResultsA total of 1756 first-visit antenatal care consultations performed by 822 providers in 648 health facilities were analyzed. The overall median [Interquartile range, IQR] adherence to first-visit antenatal care was relatively low at 47.1% [35.7%-60.5%]. After adjusting for selected variables from each level in specific strata, at dispensary; female providers [AOR = 5.5; 95% CI, 1.8-16.4], at health centre; performance of quality assurance [AOR = 2.2; 95% CI, 1.3-3.9], at hospital; availability of routine tests [AOR = 2.5; 95% CI, 1.3-4.8] and basic medicine [AOR = 2.8; 95% CI, 1.4-5.7], at public facilities; availability of medicine [AOR = 1.8; 95% CI, 1.1-3.2] and receiving refresher training [AOR = 1.8; 95% CI, 1.1-3.1], and at private facility; receiving external fund from government [AOR = 3.0; 95% CI, 1.1-8.4] were significantly associated with better adherence to first-visit antenatal care standards.ConclusionsThe study highlighted the important factors, including the provision of refresher training, regular distribution of basic medicines, and diagnostics equipment which may influence provider adherence to first-visit ANC standards.

HIV remains a public health concern in Tanzania and other Eastern and Southern African countries. Estimates show that there were about 1.4 million people living with HIV in Tanzania in the year 2013. HIV is a generalized epidemic in Tanzania with heterosexual transmission being the main route of transmission. Recently, however, there has been growing concern on the potential role of the key populations in HIV epidemic in the country. Studies done have shown significantly higher HIV prevalence in these populations compared to the general population. These studies have also reported high risky behaviors among members of these populations. This review aims at discussing the possible role of the key populations in the HIV epidemic in Tanzania.

ObjectiveThis study used a nationally representative sample from Tanzania as an example of low-resource setting with a high burden of maternal and newborn deaths, to assess the availability and readiness of health facilities to provide basic emergency obstetric and newborn care (BEmONC) and its associated factors.DesignHealth facility-based cross-sectional survey.SettingWe analysed data for obstetric and newborn care services obtained from the 2014–2015 Tanzania Service Provision Assessment survey, using WHO-Service Availability and Readiness Assessment tool.Primary and secondary outcome measuresAvailability of seven signal functions was measured based on the provision of ‘parental administration of antibiotic’, ‘parental administration of oxytocic’, ‘parental administration of anticonvulsants’, ‘assisted vaginal delivery’, ‘manual removal of placenta’, ‘manual removal of retained products of conception’ and ‘neonatal resuscitation’. Readiness was a composite variable measured based on the availability of supportive items categorised into three domains: staff training, diagnostic equipment and basic medicines.ResultsOut of 1188 facilities, 905 (76.2%) were reported to provide obstetric and newborn care services and therefore were included in the analysis of the current study. Overall availability of seven signal functions and average readiness score were consistently higher among hospitals than health centres and dispensaries (pConclusionThe study findings show disparities in the availability and readiness to provide BEmONC among health facilities in Tanzania. The Tanzanian Ministry of Health should emphasise quality assurance efforts and systematic maternal and newborn death audits. Health leadership should fairly distribute clinical guidelines, essential medicines, equipment and refresher trainings to improve availability and quality BEmONC.

Key Clinical Message Acquired HIV drug resistance following poor adherence is common. We report a case of HIV-infected patient with poor CD4 gain and self reported poor adherence. Investigations revealed high viral load and resistance to NRTIs and NNRTIs with sensitivity to boosted PIs. HIVDR mutations create treatment challenges in resource limited settings.

First described in 1925, giant condyloma acuminatum also known as Buschke-Löwenstein tumor (BLT) is a benign, slow-growing, locally destructive cauliflower-like lesion usually in the genital region. The disease is usually locally aggressive and destructive with a potential for malignant transformation. The causative organism is human papilloma virus. The most common risk factor is immunosuppression with HIV; however, any other cause of immunodeficiency can be a predisposing factor. We present a case of 33-year-old female patient, a known HIV patient on antiretroviral therapy for ten months. She presented with seven-month history of an abnormal growth in the genitalia that was progressive accompanied with foul smelling yellowish discharge and friable. Surgical excision was performed successfully. Pap smear of the excised tissue was negative. Despite being a rare condition, giant condyloma acuminatum is relatively common in HIV-infected patients.

Hepatitis B is one of the most common infectious diseases in the world with high prevalence in most of sub-Saharan Africa countries. The complexity in its diagnosis and treatment poses a significant management challenge in the resource-limited settings including Tanzania, where most of the tests and drugs are either unavailable or unaffordable. This mini review aims at demonstrating the current status of the disease in the country and discussing the concomitant challenges in diagnosis, treatment, and prevention.

Background Children and adolescents continue to have HIV/AIDS in southern Saharan Africa. Scaling up of HIV services has significantly improved access to ARV and consequently improved on morbidity and mortality related to HIV/AIDS including opportunistic infection. Despite the above efforts, non-communicable conditions including mental disorders such as depression have been observed to contribute to the burden of disabilities about which little is documented. This study, therefore, aimed to determine the magnitude of depressive symptoms and the associated factors among HIV-infected children and adolescents. Methods The study was a matched case-control design involving 300 cases of HIV-infected children matched by age and sex against 600 uninfected controls. Systematic sampling technique was used to select the cases while multistage sampling technique was employed to identify villages/ streets purposive and sampling technique was employed to obtain participants from households. Results The overall prevalence of depressive symptoms among the cohort of 900 participants was found to be 12.9%, with 27% of HIV-infected and 5.8% of HIV-uninfected children and adolescents screened positive for depressive symptoms. Multiple logistic regression revealed that being HIV-infected (AOR 1.96(1.11–3.45)), residing in a rural setting (AOR 0.61(0.39–0.96)) and history of childhood deprivation (AOR 4.76 (2.79–8.13)) were significantly associated with depressive symptoms. Conclusion HIV infected adolescents are more affected by depression compared to non-infected counterparts. Childhood deprivation was significantly associated with presence of depressive symptoms. Integration of mental health evaluation and treatment into the HIV care provided for adolescents can be beneficial. More studies to delineate factors associated with depressed adolescents with HIV may add value to the body of knowledge and overall improvement of care.

Background. Alcohol use during pregnancy is high despite the well-established evidence on its adverse pregnancy outcomes and poor child development. Early identification and behavioural modification are of great significance. This study aimed to determine the prevalence and associated factors of alcohol use during pregnancy among women in Dodoma region. Methods. 365 randomly selected pregnant women attending antenatal care services in Dodoma region were included. Structured questionnaires were used to assess sociodemographic characteristic and alcohol use. Both descriptive and inferential analyses were used to estimate the prevalence and independent relationships of factors associated with alcohol use in pregnancy, respectively. Results. Results showed a prevalence of 15.1% out of the 365 women attending antenatal services in Dodoma region. Prepregnancy alcohol use and having relatives who use alcohol were associated with alcohol use (AOR= 5.19; 95% CI: 4.791-34.867 and AOR=1.57; 95% CI: 1.393-6.248), respectively. Moreover, other associated factors included low education status (AOR=10.636; 95% CI: 1.89-19.844), making local brews as a source of income (AOR=11.44; 95% CI: 1.008-19.86), and not having had complications in previous pregnancies (AOR=4.93; 95% CI: 1.031-23.59). Conclusion. There is a significantly high prevalence of alcohol use during pregnancy in Dodoma. Social networks and low social, economic status were associated with alcohol use in pregnancy. There is a need for public health interventions to address alcohol use particularly targeting women of reproductive age with low socioeconomic status.

Background: Despite scaling up of HIV and treatment services to improve the outcome of people living with HIV, still a high proportion of patients seek out medical attention at late stages of the disease. This contributes to late initiation of ART and poor clinical outcome especially in sub Saharan Africa. The literature on magnitude of this problem in Tanzania is still scarce. This study aimed to determine the prevalence and associated factors of delayed HIV diagnosis in rural Tanzania.Methods: This was a cross sectional study, involving newly diagnosed adult HIV patients sent in for care and treatment linkage. Information regarding age, sex, WHO stage, type of opportunistic condition, HIV testing service and on diagnosis CD4 counts were all collected. On diagnosis CD4 counts

Background. Liver fibrosis which is a common complication of chronic hepatitis B infection is rarely diagnosed in low-resource countries due to limited capacity to perform biopsy studies. Data on the utilization of noninvasive techniques which are feasible for diagnosis of liver fibrosis in these settings among HIV-infected patients is scarce. The objective of this study was to establish the magnitude of liver fibrosis by using both aspartate-aminotransferase-to-platelets ratio and fibrosis-4 scores with associated hepatitis B coinfection among antiretroviral therapy naïve HIV-infected patients. Methods. We reviewed data of 743 adult patients attending HIV clinic with available hepatitis B surface antigen test results. Baseline clinical information was recorded and aspartate-aminotransferase-to-platelet ratio and fibrosis-4 scores were calculated. The cut-off values of 1.5 and 3.25 were used for diagnosis of significant fibrosis by aspartate-aminotransferase-to-platelets ratio and fibrosis-4 scores, respectively. Results. The prevalence of liver fibrosis was 3.5% when aspartate-aminotransferase-to-platelet score was used and 4.6% with fibrosis-4 score and they were both significantly higher among patients with hepatitis B coinfection. Younger patients with HIV advanced disease and elevated liver transaminases had increased risk of having hepatitis B coinfection. Conclusion. A remarkable number of HIV-infected patients present with liver fibrosis, predominantly those with hepatitis B infection.

Background Optimal HIV treatment monitoring remains a big challenge in resource limited settings. Guidelines recommend the use of clinical and immunological criteria in resource limited settings due to unavailability of viral load monitoring; however their utility is questionable. This study aimed at assessing the accuracy of immunological criteria in detecting treatment failure among HIV infected Tanzanian adults receiving first line ART. Methods A clinic based cross sectional study was conducted between February and July 2011 at Bugando Medical centre (BMC) HIV care and treatment clinic (CTC) involving HIV infected patients aged 18 years and above, receiving first line ART; followed up for at least 1 year. Viral load was tested for every enrolled patient. Standard WHO criteria were used to define immunological failure. Virological failure was defined as one viral load measurement of >5000 copies/ml and was used as a gold standard. A 2 × 2 table was used to assess the accuracy of immunological criteria in detecting treatment failure. Results A total of 274 HIV-infected adults were enrolled into the study. Out of these, 65.7% were females, the median age was 39 years (IQR 33–45), the median BMI 21.9 kg/m2 (IQR 19.7–24.0). Out of the 274 study participants 156 (56.9%) had immunological failure. Only 60 of the study participants (21.9%) had viral load >5000. Only 42 patients (70%) were found to have both immunological failure and virological failure. The sensitivity of immunological criteria in detecting treatment failure was 70%, specificity 46.7%, positive predictive and negative predictive values of 26.9 and 84.7% respectively. Conclusion WHO immunological criteria have low sensitivity and positive predictive value for detecting treatment failure. Relying on CD4 counts for treatment monitoring would therefore lead to misclassifications of treatment failure that could result into unnecessary or delayed switch to second line ART. Access to viral load monitoring is important to avoid these misclassifications.

Introduction.Smear positive TB carries high morbidity and mortality. The TB treatment aims at sputum conversion by two months of antituberculous. Patients who delay sputum conversion remain potentially infectious, with risk of treatment failure, drug resistance, and mortality. Little is known about the magnitude of this problem in our setting. This study was designed to determine the prevalence and risk factors of delayed sputum conversion in northwestern rural part of Tanzania.Methods.This was a retrospective cohort study involving smear positive TB patients at Sengerema DDH in 2015. Demographic data, HIV status, and sputum results at TB diagnosis and on TB treatment were collected and analyzed using STATA 11.Results.In total, 156 patients were studied. Males were 97 (62%); the median age was 39 [30–51] years. Fifty-five (35.3%) patients were HIV coinfected and 13 (8.3%) patients had delayed sputum conversion which was strongly associated with male gender (OR=8.2,p=0.046), age >50 years (OR=6.7,p=0.003), and AFB 3+ (OR=8.1,p=0.008).Conclusions.Delayed sputum conversion is prevalent in this study. These patients can potentially fail on treatment, develop drug resistance, and continue spreading TB. Strategies to reduce the rate of delayed sputum conversion could also reduce these potential unfavorable outcomes.

Bartholin’s gland abscess is the commonest worldwide reported abscess in gynaecological outpatient clinics; it has also been reported that Bartholin’s gland abscess is three times more common in occurrences compared to Bartholin’s gland cyst. It is more common in women who are at risk of acquiring sexually transmitted infections; however, other causes of infection should be investigated to exclude other causes of disease. We present the case of an 18-year-old female patient, a teenager of the reproductive age group, with the recurrent development of huge Bartholin’s gland abscess in a period of one year. The marsupialization surgical technique of repair was performed successfully. She was discharged home and she was scheduled to visit STI’s clinic where she was receiving regular screening for STI’s and she was also given health education regarding preventive measures for STI’s.

Globally there is an increase in the number of people living with HIV at an advanced age (50 years and above). This is mainly due to prolonged survival following the use of highly active antiretroviral therapy. Living with HIV at an advanced age has been shown to be associated with a number of challenges, both clinical and immunological. This minireview aims at discussing the challenges encountered by elderly HIV-infected patients.

Background.Limited information exists on the etiologies, clinical characteristics, and outcomes of meningitis among HIV-infected patients in Africa. We conducted a study to determine the etiology, clinical characteristics, and outcomes of meningitis among HIV-infected adults.Methods.A prospective cross-sectional hospital based study was conducted among HIV-infected patients aged ≥18 years admitted to the medical wards with symptoms and signs of meningitis. Sociodemographic and clinical information were collected using a standardized data collection tool. Lumbar puncture was performed to all patients; cerebrospinal fluid samples were sent for analysis.Results.Among 60 HIV-infected adults clinically diagnosed to have meningitis, 55 had CSF profiles consistent with meningitis. Of these, 14 (25.5%) had a laboratory-confirmed etiology while 41 (74.5%) had no isolate identified.Cryptococcus neoformanswas the commonest cause of meningitis occurring in 11 (18.3%) of patients followed byMycobacterium tuberculosis(6.7%). The in-hospital mortality was 20/55 (36.4%). Independent predictors of mortality were low baseline CD4 count and turbid CSF appearance.Conclusion.Cryptococcal meningitis is the most prevalent laboratory-confirmed etiological agent among adult HIV-infected patients with suspected meningitis admitted to medical wards in Western Tanzania. Mortality rate in this population remains unacceptably high. Improving diagnostic capacity and early treatment may help to decrease the mortality rate.

Background. Limited information exists on adults ≥50 years receiving HIV care in sub-Saharan Africa despite their increasing number. We aimed at studying immunologic and clinical responses to ART in this population. Methods. Data of patients who initiated HAART between 30th of June 2004 and 1st of May 2008 at Sekou Toure Care and Treatment Clinic were retrospectively analyzed. Date of ART initiation was used as a baseline and 48 months as a follow-up date. Immune recovery was defined as a CD4 count of ≥350 cells/mm3 at 48 months and late presentation as presentation with WHO stage 3 or 4 at clinic enrollment. Proportions of patients reaching this endpoint were compared between the two groups. Results. A total of 728 patients were included in our study; of these 73 (10.0%) were aged 50 years and above. Late presentation was more common in elderly patients than young patients (65.7% versus 56.1%, P=0.12). Proportion of patients with CD4 count ≥350 (immune recovery) was higher in younger patients than in elderly patients, although this was not statistically significant (54.5% versus 44.9%, P=0.2). Median absolute increase in CD4 at 48 months was higher in younger patients than in elderly patients (+241.5 cells/mm3 versus +146 cells/mm3, P=0.007). Conclusion. Elderly HIV patients have higher rates of late presentation, with lower immune recovery. Strategies to increase HIV testing in this group are required for early diagnosis and treatment to improve outcomes.

Introduction: Moderate to severe anemia is an important clinical problem in HIV patients on Highly Active Antiretroviral Therapy. The rate of progression and mortality in this sub group of patients is high compared to non anemic patients. In sub Saharan Africa with scale up of Anti retroviral therapy, the magnitude of this problem is not known especially in Tanzania. This study aimed at determining the magnitude and correlates of moderate to severe anemia in HIV patients receiving first line ART in northwestern Tanzania. Methods: This was a cross sectional clinic based study, involving adult HIV patients on first line Highly Active Antiretroviral Therapy at Bugando Medical Centre Care and Treatment Center. The patients' data were analyzed using STATA version 11 to determine the prevalence of moderate to severe anemia and risk factors that could predict occurrence of anemia. Results: In this study 346 patients on Highly Active Anti-Retroviral Therapy were enrolled, of whom 100(40.46%) had moderate to severe anemia. The odds of being anemic were strongly predicted by Zidovudine based regime, low baseline CD4 count (< 200 cells/μl) and HIV stage 3&4 at enrollment. Most of the anemic patients had mean corpuscular volume of >100fl. Conclusion: The prevalence of moderate to severe anemia is significantly high in this cohort of HIV-infected patients on first line Anti Retroviral Therapy and it is strongly predicted by Zidovudine based regime, low baseline CD4 and HIV stage 3 and 4. On clinical grounds this suggests that patients who are initiated on Zidovudine based regimen and those in advanced HIV at enrollment should have regular haemoglobin follow up to identify anemia at its earliest stage to improve the clinical outcome of these patients.Pan African Medical Journal 2016; 23

Objective: To evaluate the family history of epilepsy in first degree relatives of probands with epilepsy. Methods: A sample of 10787 patients with epilepsy with complete information about first degree relatives (parents, siblings and offspring) was selected from the database of the Episcreen Project, the largest Italian observational study on epilepsy. Family history was assessed by: (1) prevalence estimates of epilepsy among proband's relatives, (2) modified cumulative risks (MCR), adjusted using proband's age as censoring time in life tables, (3) standardised morbidity ratios (SMR), using a sub-group of symptomatic epilepsies as control group. Results: Patients (9.1%) had a family history of epilepsy. The overall prevalence of epilepsy among first degree relatives was 2.6%. Idiopathic generalised epilepsies had the highest prevalence (5.3%). Cryptogenetic epilepsies had a lower prevalence (2.1%) than idiopathic epilepsies, but higher then symptomatic epilepsies (1.5%), both in generalised and focal forms (3.8% vs. 2.0% and 1.8% vs. 1.3%). A similar tendency was detected using MCR and SMR, with the higher values of risks/ratios for idiopathic and generalised epilepsies. Probands with idiopathic generalised epilepsies were highly concordant with respect to their relatives' type of epilepsy. Considering other strata factors, risks were higher in proband's epilepsies with an onset less then 14 years of age, while sex played no definite role in differentiating the family history. Conclusions: The Episcreen model permits a variety of stratification factors to measure family risk, including age at onset, epilepsy localisation and aetiology with a large sample of more than 10000 probands and 1065/40544 relatives affected and classified.

Introduction Sub-Saharan Africa is experiencing a rapid rise in the burden of non-communicable diseases in both urban and rural areas. Data on health system preparedness to manage hypertension and other non-communicable diseases remains scarce. This study aimed to assess the preparedness of lower-level health facilities for outpatient primary care of hypertension in Tanzania. Methods This study used data from the 2014–2015 Tanzania Service Provision Assessment survey. The facility was considered as prepared for the outpatient primary care of hypertension if reported at least half (≥50%) of the items listed from each of the three domains (staff training and guideline, basic diagnostic equipment, and basic medicines) as identified by World Health Organization-Service Availability and Readiness Assessment manual. Data were analyzed using Stata 14. An unadjusted logistic regression model was used to assess the association between outcome and explanatory variables. All variables with a P value < 0.2 were fitted into the multiple logistic regression models using a 5% significance level. Results Out of 725 health facilities involved in the current study, about 68% were public facilities and 73% located in rural settings. Only 28% of the assessed facilities were considered prepared for the outpatient primary care of hypertension. About 9% and 42% of the assessed facilities reported to have at least one trained staff and guidelines for hypertension respectively. In multivariate analysis, private facilities [AOR = 2.7, 95% CI; 1.2–6.1], urban location [AOR = 2.2, 95% CI; 1.2–4.2], health centers [AOR = 5.2, 95% CI; 3.1–8.7] and the performance of routine management meetings [AOR = 2.6, 95% CI; 1.1–5.9] were significantly associated with preparedness for the outpatient primary care of hypertension. Conclusion The primary healthcare system in Tanzania is not adequately equipped to cope with the increasing burden of hypertension and other non-communicable diseases. Rural location, public ownership, and absence of routine management meetings were associated with being not prepared. There is a need to strengthen the primary healthcare system in Tanzania for better management of chronic diseases and curb their rising impact on health outcomes.

Background: HIV/AIDS causes high morbidity and mortality through both immunosuppression and complications not directly related to immunosuppression. Haematological abnormalities, including various cytopenias, occur commonly in HIV through immune and non-immune pathways. Though these complications could potentially cause serious clinical implications, published literature on the magnitude of this problem and its associated factors in Tanzania is scarce. This study aimed at determining the prevalence and risk factors of HIV-associated cytopenias among ART-naive patients enrolling for care and treatment services at Bugando Care and Treatment Centre (CTC) in Mwanza, Tanzania. Methods: This was a cross-sectional clinic-based study done between March 2015 and February 2016, involving all antiretroviral therapy (ART)-naive adult HIV positive patients enrolling for care and treatment services at Bugando CTC. Patients younger than 18 years and those with missing data were excluded. Data were analysed using Stata version 11 to determine the prevalence and risk factors of cytopenias. Results: A total of 1205 ART-naive patients were included. Median age was 41 years (interquartile range [IQR] 32 to 48). Most participants were female (n = 789; 65.6%), with a female-to-male ratio of 2:1. The median baseline CD4 count was 200 cells/μL (IQR 113 to 439). About half (49%) of the study participants had baseline CD4 counts less than 200 cells/μL. Anaemia, leucopenia, and thrombocytopenia were found in 704 (58.4%), 285 (23.6%), and 174 (14.4%) participants, respectively, and these were strongly associated with advanced HIV infection. Conclusions: The magnitude of cytopenias is high among ART-naive HIV-positive adults, and cytopenias are more marked with advanced HIV infection. Early diagnosis of HIV and timely initiation of ART could potentially reduce the number of people living with advanced HIV disease and its associated complications, including the cytopenias investigated in this study. Patients with cytopenias should undergo thorough screening for tuberculosis, which is an important and treatable correlate of cytopenia, in addition to close follow-up for any potential negative outcomes.

Summary Objective: Eyelid myoclonia with absences (EMA) or Jeavons syndrome characterized by eyelid myoclonia (EM) (with or without absences), eye closure-induced EEG paroxysms, and photosensitivity. We conducted an open-label trial of levetiracetam in EMA. Patients and Methods: Patients were recruited in different Italian Epilepsy Centres. Levetiracetam was administrated at starting dose of 10 mg/kg/day up to 50–60 mg/kg/day in two doses. Treatment period included a 5–6 week up-titration phase and a 12-week evaluation phase. The number of days with EM (i.e., days with seizures, DwS) and number of generalized tonic–clonic seizures (GTCS) were evaluated. Analysis of intent-to-treat population was performed using Fisher's and Wilcoxon tests. Results: Thirty-five patients (23 F) with a mean age of 19 ± 6 years were recruited. Twenty-seven had previously undergone one to five adequate trials of antiepileptic drugs. The median number of DwS/month was 12 ± 8.2. Twenty-one patients experienced GTCS (median number/month: 1 ± 0.2). Thirty-four subjects completed the trial. Levetiracetam was well tolerated (mean dose: 1985 mg/day). Responders were 28/35 (80%) patients, nine taking levetiracetam as monotherapy. Six patients were seizure-free, 15 had ≥75% and seven >50% seizure reduction. GTCS remitted in 14 out of 21 (66.6%) patients. The number/month of DwS (median: 12 vs 5; p = 0.0001) and of GTCS (median: 1 vs 0; p = 0.0001) decreased compared to baseline period. Disappearance or clear reduction in paroxysmal abnormalities at eye closure occurred in 20 of the responders and photoparoxysmal response in 19. Mean follow-up was 23.9 ± 18.5 months. Conclusion: Levetiracetam is effective and well tolerated in EMA. Placebo-controlled studies should confirm these findings.

Gestational diabetes mellitus (GDM) is a well-characterized disease affecting a significant population of pregnant women worldwide. It has been widely linked to undue weight gain associated with factors such as diet, obesity, family history, and ethnicity. Poorly controlled GDM results in maternal and fetal morbidity and mortality. Improved outcomes therefore rely on early diagnosis and tight glycaemic control. While straightforward protocols exist for screening and management of diabetes mellitus in the general population, management of GDM remains controversial with conflicting guidelines and treatment protocols. This review highlights the diagnostic and management options for GDM in light of recent advances in care.

Objectives Cognitive abilities and executive functions in children and adolescents are important indicators of quality of life as well as academic and social achievements. Cognitive and executive functioning are often impaired in patients with epilepsy and can be exacerbated by seizures and antiseizure drugs. The aim of our observational retrospective study was to assess executive functioning in patients with pediatric epilepsy, currently taking a single antiseizure medication. Materials and methods Records of 172 children and adolescents aged between 6 and 18 years (mean age = 12 ± 3.4 years) with newly diagnosed epilepsy who had not yet commenced an antiepileptic treatment were included in the study. Longitudinal changes in executive functioning were assessed using the EpiTrack Junior test at baseline, before the introduction of antiepileptic monotherapy, and at 3-month, 6-month, and 9-month follow-up visits. All patients commenced a single antiepileptic treatment (levetiracetam n = 54; valproic acid n = 52; ethosuximide n = 20; oxcarbazepine n = 22; carbamazepine n = 24). Age, sex, seizure types, and seizure baseline frequency were also recorded. Results Relative to baseline, Epitrack Junior mean scores deteriorated at the 9-month follow-up visit for patients taking valproic acid, ethosuximide, and carbamazepine, but this was only statistically significant for patients taking carbamazepine. In contrast, mean scores improved for subjects taking levetiracetam and oxcarbazepine at the 9-month follow-up visit relative to baseline, but this was only statistically significant for patients taking levetiracetam. Conclusions Levetiracetam was the only antiseizure medication that led to slight improvements in executive functioning; whereas carbamazepine led to deteriorations in cognitive functioning. Further research using double-blinded, placebo-controlled trials are needed to confirm these results.

Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. Conclusions A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics.

Epilepsy is a pathologic condition with high prevalence and devastating consequences for the patient and its entourage. Means for accurate diagnosis of type, patient monitoring for predicting seizures and follow up, and efficacious treatment are desperately needed. To improve this adverse outcome, miRNAs and the chaperone system (CS) are promising targets to understand pathogenic mechanisms and for developing theranostics applications. miRNAs implicated in conditions known or suspected to favor seizures such as neuroinflammation, to promote epileptic tolerance and neuronal survival, to regulate seizures, and others showing variations in expression levels related to seizures are promising candidates as useful biomarkers for diagnosis and patient monitoring, and as targets for developing novel therapies. Components of the CS are also promising as biomarkers and as therapeutic targets, since they participate in epileptogenic pathways and in cytoprotective mechanisms in various epileptogenic brain areas, even if what they do and how is not yet clear. The data in this review should help in the identification of molecular targets among the discussed miRNAs and CS components for research aiming at understanding epileptogenic mechanisms and, subsequently, develop means for predicting/preventing seizures and treating the disease.

Purpose: Recently, altered visual cortical processes i.e., lack of habituation to visual evoked potentials (VEP), has been highlighted in both photosensitive epilepsy and in a specific i.e., analytic mode of processing visual inputs. In this study we aimed at evaluating the relationship between photosensitivity (PS) and analytic style of processing visual information, in a sample of 30 patients with Idiopathic Generalized Epilepsy (IGE) and matched healthy controls. Methods: At our Epilepsy unit of the Sapienza University of Rome, we consecutively enrolled 15 patients with IGE with PSand matched them with 15 patients with IGE without PS and 15 Healthy Volunteers. All patients underwent EEG recording in basal conditions during hyperventilation (3 Min), and intermittent light stimulation. The most effective frequencies comprised from 12 to 16 Hz. The instruments used to gather psychological cognitive behavioral data, consisted of participation in two tests: the Sternberg-Wagner Self-Assessment Inventory and the Mariani Learning Style Questionnaire. Results: Compared to controls, both IGE groups show significantly higher scores for the analytic style (One-way ANOVA, F(2,44) = 110.3, p < 0.0001). Epilepsy groups thereby showed very distinctive cognitive styles as measured with the Sternberg test. In the visual style, scores of the photosensitive Individuals with IGE were significantly higher than the non-photosensitive individuals with IGE (p < 0.0001, Tukey's post hoc test). Conclusions: An association between analytic style of processing visual information and PS in IGE has been shown. The common neurophysiological features between these two factors, suggest the possibility to evaluate this cognitive behavior as a potential target for nonpharmacological therapeutic strategies in photosensitive epilepsy.

Objectives Perampanel (PER) is a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist recently approved for focal and generalized epilepsies as an add-on therapy. It is well tolerated and effective as treatment of various pediatric epilepsy syndromes; PER does not seem to negatively affect the cognitive profile of children and adolescents, but its influence on executive functions is still to be assessed. Methods Our sample included 37 children aged 12–18 years, with focal pharmacoresistant epilepsy already in therapy with 2 or 3 antiepileptic drug (AED); PER was added with 1 mg/week increments up to a dose of 2–4 mg/day. Changes in executive functions were assessed by the EpiTrack Junior test. Emotional and behavioral aspects were evaluated through the interview for parents Child Behavior Checklist (CBCL). Both tests were performed before taking PER and after 6 and 12 months of treatment. Results After 12 months of PER in 22/30 patients, global score of the EpiTrack Junior test remained almost unchanged; in 7/30 patients, this score improved. The CBCL did not show significant changes in emotional or behavioral problems. Conclusions Adjunctive treatment with PER did not negatively affect executive functions that could also be improved. No emotional/behavioral negative effects have been reported, and this suggests a good tolerability in the middle/long term.

Background: Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients. Material and methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included. Results: Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies. Conclusions: Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.

Background and purpose The presence of a continuum between physiological deja vu (DV) and epileptic DV is still not known as well as epidemiological data in the Italian population. The aim was to identify the epidemiological distribution of DV in Italy, and secondly to look for specific features of DV able to discriminate between epileptic and non-epileptic DV. Methods In all, 1000 individuals, 543 healthy controls (C) (313 women; age 40 ± 15 years) and 457 patients with epilepsy (E) (260 women; age 39 ± 14 years), were prospectively recruited from 10 outpatient neurological clinics throughout Italy. All populations were screened using the Italian Inventory for Deja Vu Experiences Assessment (I-IDEA) test and E and pairwise C underwent a comprehensive epilepsy interview. Results Of E, 69% stated that they experienced 'recognition' and 13.2% reported that this feeling occurred from a few times a month to at least weekly (versus 7.7% of the control group). Furthermore, a greater percentage of E (6.8% vs. 2.2%) reported that from a few times a month to at least weekly they felt that it seemed as though everything around was not real. In E, the feeling of recognition raised fright (22.3% vs. 13.2%) and a sense of oppression (19.4% vs. 9.4%). A fifth of E felt recognition during epileptic seizures. Conclusion Only E regardless of aetiology firmly answered that they had the feeling of recognition during an epileptic seizure; thus question 14 of the I-IDEA test part 2 discriminated E from C. Paranormal activity, remembering dreams and travel frequency were mostly correlated to DV in E suggesting that the visual-memory network might be involved in epileptic DV.

Purpose Gluten-related disorders (GRDs) are a group of immune-mediated diseases often associated to neurologic manifestations. Epilepsies with cerebral calcifications, with or without coeliac disease (CD), are rare neurological disorders characterized by childhood-onset focal seizures, often refractory to antiepileptic drugs. Transglutaminase 6 antibodies (anti-TG6) have been considered a biomarker for gluten-related ataxia and neuropathy, but their prevalence in epilepsies with cerebral calcifications is unknown. The aim of this study is to evaluate anti-TG6 prevalence in patients with epilepsies and cerebral calcifications. Method this was a cross-sectional study conducted at five Italian epilepsy centres. The following groups were included. Group 1: nine patients with CD, posterior cerebral calcifications and epilepsy (CEC); group 2: nine patients with epilepsy and posterior cerebral calcifications, without CD; group 3: twenty patients with focal epilepsy of unknown etiology; group 4: twenty-two healthy controls (HC). All subjects were tested for serological evidence of anti-TG6 IgA and IgG. Differences among groups were analysed using χ ² test. Results anti-TG6 were present in 1/9 subjects (11%) of group 1, 2/9 subjects (22%) of group 2, 0/20 subjects in group 3, 3/22 (13.6%) of HC. No significant difference was found among the 4 groups. Conclusions Anti-TG6 do not seem to be associated to epilepsies with cerebral calcifications.

Summary Purpose Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by prominent auditory or aphasic symptoms. Mutations in LGI1 account for less than 50% of ADLTE families. We assessed the impact of LGI1 microrearrangements in a collection of ADLTE families and sporadic lateral temporal epilepsy (LTE) patients, and investigated novel ADLTE and LTE patients. Methods Twenty-four ADLTE families and 140 sporadic LTE patients with no evidence of point mutations in LGI1 were screened for copy number alterations using multiplex ligation-dependent probe amplification (MLPA). Newly ascertained familial and sporadic LTE patients were clinically investigated, and interictal EEG and MRI findings were obtained; probands were tested for LGI1 mutations by direct exon sequencing or denaturing high performance liquid chromatography. Results We identified a novel microdeletion spanning LGI1 exon 2 in a family with two affected members, both presenting focal seizures with visual symptoms. Also, we identified a novel LGI1 missense mutation (c.1118T>C; p.L373S) in a newly ascertained family with focal seizures with prominent visual auras, and another missense mutation (c.856T>C; p.C286R) in a sporadic patient with auditory seizures. Conclusions We describe two novel ADLTE families with predominant visual auras segregating pathogenic LGI1 mutations. These findings support the notion that, in addition to auditory symptoms, other types of auras can be found in patients carrying LGI1 mutations. The identification of a novel microdeletion in LGI1 , the second so far identified, suggests that LGI1 microrearrangements may not be exceptional.

The aim of the present study was to evaluate the Epi-QoL, a new Italian-specific measure of health-related quality of life (HRQOL) for adults with epilepsy; the clinical variables that affected the HRQOL score were also assessed. The Epi-QoL is a 46-item self-administered questionnaire focusing on six domains: Physical Functioning, Cognitive Functioning, Emotional Well-Being, Social Functioning, Seizure Worry, and Medication Effects. Eight hundred fifteen patients recruited from 24 secondary and tertiary Italian centers for the care of epilepsy were assessed. The results supported the reliability and validity of the Epi-QoL as a measure of HRQOL. The variables that significantly affected HRQOL scores were: geographic area, gender, seizure frequency, prognostic categories, number of medications, comorbidity, presence of cognitive impairment, psychiatric disturbances, and disability. We believe that a new specific questionnaire for the evaluation of HRQOL in Italy can contribute much to the understanding of the influence of epilepsy on patients' lives.