Mother-to-child transmission of HIV : When a child inherits HIV from its mother

The thesis comprises a literature review, a histopathology study of placentas from Kenya in addition to observations and reflections from a field study in primary health care clinics in Moshi, Tanzania. Transmission of HIV from a HIV-positive woman to her unborn child or infant is defined as Mother-To-Child-Transmission, MTCT. The virus can be transmitted during pregnancy, delivery or after birth through breast milk. Ante partum transmission can take place blood borne through placenta or ascending from cervico-vaginal secretions. Morphologically the placentas of HIV-positives show higher incidence of chorioamnionitis. There are no placental changes known as specific HIV-features. Three interventions are proven efficient in reducing the MTCT. They are antiretroviral therapy to the woman before and during delivery and to the newborn, caesarean section and avoiding breastfeeding, alternatively exclusive breastfeeding. In industrialized countries these interventions have reduced the MTCT-rate from up to 45% to less than 2%. WHO estimate that more than 40 million people currently live with HIV/AIDS. 25-28 million of these live in Sub-Saharan Africa, including over 2 million infected in Tanzania. Several years with HIV focus by the Tanzanian government and increasing international and private support have resulted in programs for fighting the HIV epidemic, including national pilot programs against MTCT. In June/July 2003 I worked in an ongoing local MTCT pilot program in health clinics in Moshi, a small town close to Kilimanjaro. I observed HIV s role and influence in an African community and how health personnel handled the problem with limited resources. Despite international engagement, improved financing and focus on HIV, the HIV-fighting programs in developing countries have not showed the expected results. HIV is still spreading and the situation is far from being under control. Efficient use of financial resources is threatened by capacity shortfalls in health service systems at district level, lack of health- and administrative personnel as well as dysfunctional infrastructure. An even larger problem is low compliance in populations to use services being offered in HIV-programs. Lack of knowledge and delusions influenced by local culture, religion and witchcraft have been identified. Stigma however, is the most important obstacle to compliance. HIV is still associated with personal guilt and shame. HIV-positives are maltreated and discriminated in their local community. People thus often choose not to tell they are infected. They don t use preventive methods as condoms and they breastfeed their children to avoid rumours in the community. People additionally consider HIV-infection as a death sentence no point knowing. Primary prevention to avoid HIV-infection must be the global number one goal, also in the work against MTCT. In order to succeed in HIV-combat programs it is also important to eradicate stigma, demystify HIV/AIDS, focus on human rights and support the HIV-infected to give them hope for a decent future

‘No service is an island’: experiences of collaboration with crisis resolution teams in Norway

Crisis resolution teams (CRTs) are a community-based service targeting adults experiencing acute mental health crises. The rationale for the development of CRTs is both value and efficacy based, suggesting that CRTs should contribute to the humanizing of mental health services and replace some acute hospital-based services with services in the community. Despite the collaborative nature of CRT work, how professionals from health and social services experience collaboration with CRTs is scantly explored. In the current study, semi-structured focus group interviews with eight different groups of 44 clinicians collaborating with CRTs in Norway were conducted. Data were analyzed using thematic analysis and categorized into four themes: (1) ‘The accessible experts’, (2) ‘A broad and deep expertise’, (3) ‘Doing it together’ and (4) ‘Toward a new culture?’. The themes elaborate on issues related to the content and organization of CRT services, emphasizing the need for CRTs to be able to contribute their professional expertise in accessible, flexible and collaborative ways. A diversity in the knowledge base and in how services are organized may pose a challenge in interprofessional mental health crisis collaboration and mutual expectations. The study suggests that a shift toward a value-based and coherent mental health and social system could be a purposeful direction

‘No service is an island’: experiences of collaboration with crisis resolution teams in Norway

Crisis resolution teams (CRTs) are a community-based service targeting adults experiencing acute mental health crises. The rationale for the development of CRTs is both value and efficacy based, suggesting that CRTs should contribute to the humanizing of mental health services and replace some acute hospital-based services with services in the community. Despite the collaborative nature of CRT work, how professionals from health and social services experience collaboration with CRTs is scantly explored. In the current study, semi-structured focus group interviews with eight different groups of 44 clinicians collaborating with CRTs in Norway were conducted. Data were analyzed using thematic analysis and categorized into four themes: (1) ‘The accessible experts’, (2) ‘A broad and deep expertise’, (3) ‘Doing it together’ and (4) ‘Toward a new culture?’. The themes elaborate on issues related to the content and organization of CRT services, emphasizing the need for CRTs to be able to contribute their professional expertise in accessible, flexible and collaborative ways. A diversity in the knowledge base and in how services are organized may pose a challenge in interprofessional mental health crisis collaboration and mutual expectations. The study suggests that a shift toward a value-based and coherent mental health and social system could be a purposeful direction

Exercise is Associated With Impaired Left Ventricular Systolic Function in Patients With Lamin A/C Genotype

Background Lamin A/C cardiomyopathy is a malignant and highly penetrant inheritable cardiomyopathy. Competitive sports have been associated with adverse events in these patients, but data on recreational exercise are lacking. We aimed to explore associations between exercise exposure and disease severity in patients with lamin A/C genotype. Methods and Results Lamin A/C genotype positive patients answered a questionnaire on exercise habits from age 7 years until genetic diagnosis. We recorded exercise hours >3 metabolic equivalents and calculated cumulative lifetime exercise. Patients were grouped in active or sedate based on lifetime exercise hours above or below median. We performed echocardiography, 12‐lead ECG, Holter monitoring, and biomarkers including NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide). We defined left ventricular ejection fraction <45% as a clinically significant impairment of left ventricular function. We included 69 patients (age 42±14 years, 41% probands, 46% women) with median lifetime exercise 4160 (interquartile range 1041–6924) hours. Active patients were more frequently probands (53% versus 29%, P=0.04), had lower left ventricular ejection fraction (43±13% versus 51±11%, P=0.006), and higher NT‐proBNP (78 [interquartile range 32–219] pmol/L versus 30 [interquartile range 13–64] pmol/L, P=0.03) compared with sedate, while age did not differ (45±13 years versus 40±16 years, P=0.16). The decrease in left ventricular ejection fraction per tertile increment in lifetime exercise was 4% (95% CI −7% to −0.4%, P=0.03), adjusted for age and sex and accounting for dependence within families. Left ventricular ejection fraction <45% was observed at a younger age in active patients (log rank P=0.007). Conclusions Active lamin A/C patients had worse systolic function compared with sedate which occurred at younger age. Our findings may improve exercise recommendations in patients with lamin A/C

Lamin A/C cardiomyopathy: Young onset, high penetrance, and frequent need for heart transplantation

Aims: Lamin A/C (LMNA) mutations cause familial dilated cardiomyopathy (DCM) with frequent conduction blocks and arrhythmias. We explored the prevalence, cardiac penetrance, and expressivity of LMNA mutations among familial DCM in Norway. Furthermore, we explored the risk factors and the outcomes in LMNA patients. Methods and results: During 2003–15, genetic testing was performed in patients referred for familial DCM. LMNA genotype-positive subjects were examined by electrocardiography, Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. A positive cardiac phenotype was defined as the presence of atrioventricular (AV) block, atrial fibrillation/flutter (AF), ventricular tachycardia (VT), and/or echocardiographic DCM. Heart transplantation was recorded and compared with non-ischaemic DCM of other origin. Of 561 unrelated familial DCM probands, 35 (6.2%) had an LMNA mutation. Family screening diagnosed an additional 93 LMNA genotype-positive family members. We clinically followed up 79 LMNA genotype-positive [age 42 ± 16 years, ejection fraction (EF) 45 ± 13%], including 44 (56%) with VT. Asymptomatic LMNA genotype-positive family members (age 31 ± 15 years) had a 9% annual incidence of a newly documented cardiac phenotype and 61% (19/31) of cardiac penetrance during 4.4 ± 2.9 years of follow-up. Ten (32%) had AV block, 7 (23%) AF, and 12 (39%) non-sustained VT. Heart transplantation was performed in 15 of 79 (19%) LMNA patients during 7.8 ± 6.3 years of follow-up. Conclusion: LMNA mutation prevalence was 6.2% of familial DCM in Norway. Cardiac penetrance was high in young asymptomatic LMNA genotype-positive family members with frequent AV block and VT, highlighting the importance of early family screening and cardiological follow-up. Nearly 20% of the LMNA patients required heart transplantation

Vigorous physical activity impairs myocardial function in patients with arrhythmogenic right ventricular cardiomyopathy and in mutation positive family members

Aims: Exercise increases risk of ventricular arrhythmia in subjects with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to investigate the impact of exercise on myocardial function in ARVC subjects. Methods and Results: We included 110 subjects (age 42±17 years), 65 ARVC patients and 45 mutation-positive family members. Athletes were defined as subjects with ≥4 h vigorous exercise/week [≥1440 metabolic equivalents (METs × minutes/week)] during a minimum of 6 years. Athlete definition was fulfilled in 37/110 (34%) subjects. We assessed right ventricular (RV) and left ventricular (LV) myocardial function by echocardiography, and by magnetic resonance imaging (MRI). The RV function by RV fractional area change (FAC), RV global longitudinal strain (GLS) by echocardiography, and RV ejection fraction (EF) by MRI was reduced in athletes compared with non-athletes (FAC 34±9% vs. 40±11%, RVGLS –18.3±6.1% vs. –22.0±4.8%, RVEF 32±8% vs. 43±10%, all P<0.01). LV function by LVEF and LVGLS was reduced in athletes compared with non-athletes (LVEF by echocardiography 50±10% vs. 57±5%, LVEF by MRI 46±6% vs. 53±8%, and LVGLS –16.7±4.2% vs. –19.4±2.9%, all P <0.01). The METs × minutes/week correlated with reduced RV and LV function by echocardiography and MRI (all P <0.01). The LVEF by MRI was also reduced in subgroups of athlete index patients (46±7% vs. 54±10%, P=0.02) and in athlete family members (47±3% vs. 52±6%, P <0.05). Conclusion: Athletes showed reduced biventricular function compared with non-athletes in ARVC patients and in mutation-positive family members. The amount and intensity of exercise activity was associated with impaired LV and RV function. Exercise may aggravate and accelerate myocardial dysfunction in ARVC