Cystometric urine stream interruption test in women with urodynamic stress incontinence.

Urine stream interruption test (UST) is one of the subjective means of assessing pelvic floor muscle strength. This is done with the belief that most women with stress urinary incontinence cannot interrupt the flow of urine stream due to weak pelvic floor muscles. It is also used by some to monitor pelvic floor muscle strength following treatment. Our study looked at a cohort of 104 women with stress urinary incontinence and to our knowledge, our study is the first to use UST in women who have had their stress urine incontinence confirmed on urodynamics. We found that 87% of those with urodynamic stress incontinence (USI) were able to perform this test (UST). We therefore concluded that UST is a poor index of pelvic floor muscle function in women with USI and cannot be relied upon to monitor success of treatment in these women.     

Sociodemographic Characteristics and Drug Abuse Patterns of Treatment-Seeking Illicit Drug Abusers in Finland, 1997–2008: The Huuti Study

The epidemiological part of the Huume tietokanta (HUUTI) consortium research project is the first large-scale longitudinal study of treatment-seeking illicit drug abusers in Finland. The objective of this report was to describe the sociodemographic characteristics and drug abuse patterns of treatment-seeking clients at their first visit. This study analysed baseline data of 4817 clients (3365 men and 1452 women) aged 11–65 years who sought treatment for drug abuse between 1997 and 2008 at Helsinki Deaconess Institute. Data were collected using a structured questionnaire. The majority (56%) of clients were between 15 and 24 years, educated at elementary school level (75%), and unemployed (57%). Opiates (30%) were the primary drugs of abuse. The primary drugs were mostly injected (45%) and were abused daily during the past month (44%). Cannabis was the most common secondary drug of abuse (34%). The secondary drugs were predominantly smoked (39%) or taken orally (38%) and were abused once per week or less frequently during the past month (33%). Age at initiation of illicit drug abuse ranged from 5 to 49 years. Polydrug abuse was common, with a mean consumption of 3.5 concurrent polydrug use, which were combined from 3 or more drug classes. The prevalence of lifetime/ever intravenous drug abuse was 64% and past month intravenous drug abuse was 64%, respectively, and 13% reported sharing injecting equipment during the past month. Early initiation, polydrug abuse, and risky consumption of illicit drugs were major areas of concern among the study population. Injecting drug use could place considerable burden on health services in view of complications and transmission of infectious diseases.     

Chronic HIV infection and health related quality of life in resource poor settings-an assessment from South East Nigeria

BackgroundHealth-related quality of life reflects a patient''s general subjective perception of the effect of an illness or intervention on physical, psychological and social aspects of daily life. HIV infection is a major public health problem especially in developing countries where poor health infrastructure and poverty are prevalent. This paper addresses the quality of life in patients with chronic HIV infection in South East Nigeria and addresses issues that may help improve the current situation.MethodsA cross-sectional survey was carried out at the University of Nigeria Teaching Hospital, Enugu, to assess patients with HIV receiving antiretroviral therapy (ART) using a validated structured questionnaire (WHOQoL-BREF). Ethical clearance for the study was obtained. Study period was from October - December, 2017. Data obtained was analysed.ResultsA total of 389 HIV patients consented to the study. Over 70% were aged 18- 45 years and majority were females. Females had a higher quality of life score with respect to the domain of psychological health while males had a higher score with respect to the environmental domain. Older age and presence of co-morbidities were significantly associated with affectation of physical health while younger age was associated with affectation of psychological health domain.ConclusionHIV impairs the quality of life for affected individuals in South East Nigeria especially across the domains of physical and psychological health. No age group is spared. The presence of co-morbidities significantly reduces quality of life in these patients. Younger patients may require mental health services in the management of their disease.     

Efficacy of venetoclax in high risk relapsed mantle cell lymphoma (MCL) - outcomes and mutation profile from venetoclax resistant MCL patients

Venetoclax is effective in relapsed patients with mantle cell lymphoma (MCL). Mechanisms of resistance to venetoclax in MCL are poorly understood. We describe the clinical outcomes and genomic characteristics of 24 multiply relapsed patients (median of five prior lines of therapy) who received venetoclax-based therapies; 67% had progressed on BTK inhibitors (BTKi) and 54% had blastoid or pleomorphic histology. Median follow up after venetoclax treatment was 17 months. The overall response rate was 50% and complete response (CR) rate was 21%, 16 patients had progressed and 15 died. The median progression free, overall and post venetoclax survival were 8, 13.5 and 7.3 months respectively. Whole-exome sequencing (WES) was performed on samples collected from seven patients (including five pairs; before starting venetoclax and after progression on venetoclax). The SMARCA4 and BCL2 alterations were noted only after progression, while TP53, CDKN2A, KMT2D, CELSR3, CCND1, NOTCH2 and ATM were altered 2-4-fold more frequently after progression. In two patients with serial samples, we demonstrated clonal evolution of novel SMARCA4 and KMT2C/D mutations at progression. Mutation dynamics in venetoclax resistant MCL is demonstrated. Our data indicates that venetoclax resistance in MCL is predominantly associated with non-BCL2 gene mutations. Further studies are ongoing in MCL patients to evaluate the efficacy of venetoclax in combination with other agents and understand the biology of venetoclax resistance in MCL.     

Boerhaave's syndrome presenting as tension pneumothorax.

Boerhaave's syndrome can present initially as a case of tension pneumothorax. Mortality rate with delayed treatment is very high, therefore diagnosis should be made rapidly in the emergency department. Multidisciplinary cooperation, immediate radiological confirmation, prompt aggressive resuscitation, and surgical intervention offer the best chance of survival.     

Synthesis of some cryptolepine analogues, assessment of their antimalarial and cytotoxic activities, and consideration of their antimalarial mode of action

A series of analogues of cryptolepine (1) have been synthesized and evaluated for their in vitro antiplasmodial and cytotoxic properties. The IC(50) values of several compounds (11a, 11k-m, 11o, 13) against Plasmodium falciparum (strain K1) were <0.1 muM, 5-10-fold lower than that of 1 but their cytotoxicities were only 2-4 times greater than that of 1. Compounds with a halogen in the quinoline ring and a halogen or a nitro group in the indole ring have enhanced antiplasmodial activity. In mice infected with P. berghei, the 7-bromo-2-chloro (11k) and 2-bromo-7-nitro (13) derivatives of 1 suppressed parasitemia by >90% at doses of 25 mg kg(-1) day(-1) with no apparent toxicity to the mice. 2,7-Dibromocryptolepine (15) was evaluated at several dose levels, and a dose-dependent suppression of parasitemia was seen (ED(90) = 21.6 mg kg(-1) day(-1)). The antimalarial mode of action of 1 appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation. A number of analogues were assessed for their effects on the inhibition of beta-hematin (hemozoin) formation, and the results were compared with their antiplasmodial activities having taken account of their predicted accumulation into the acidic parasite food vacuole. No correlation was seen (r(2) = 0.0781) suggesting that the potent antimalarial activity of compounds such as 15 involves other mechanisms in addition to the inhibition of hemozoin formation.