Enhancing the management of long COVID in general practice: a scoping review.

BACKGROUND: Long COVID is a multifaceted condition, and it has impacted a considerable proportion of those with acute COVID-19. Affected patients often have complex care needs requiring holistic and multidisciplinary care, the kind routinely provided in general practice. However, there is limited evidence regarding GP interventions. AIM: This study aimed to identify key concepts and knowledge gaps around long COVID by conducting a scoping review of literature on the condition's management by GPs. DESIGN & SETTING: Arksey and O'Malley's six-stage scoping review framework, with recommendations by Levac et al, was used. METHOD: PubMed, Google Scholar, the Cochrane Library, Scopus, and Google searches were conducted to identify relevant peer reviewed and grey literature, and study selection process was conducted according to the PRISMA Extension for Scoping Reviews guidelines. Braun and Clarke's 'Thematic Analysis' approach was used to interpret data. RESULTS: Nineteen of 972 identified articles were selected for review. These included peer reviewed articles and grey literature spanning a wide range of countries. Six themes were identified regarding GP management of long COVID, these being: (1) GP uncertainty, (2) listening and empathy, (3) assessment and monitoring of symptoms, (4) coordinating access to appropriate services, (5) facilitating provision of continual and integrated multidisciplinary care and (6) need to provide or facilitate psychological support. CONCLUSION: The findings show that GPs can play and have played a key role in the management of long COVID, and that patient care can be improved through better understanding of patient experiences, standardised approaches for symptom identification and treatment, and facilitation of access to multidisciplinary specialist services when needed. Future research evaluating focused GP interventions is needed.

High rate of unplanned pregnancy in the context of integrated family planning and HIV care services in South Africa.

BACKGROUND: Integration of family planning services into HIV care was implemented in South Africa as a core strategy aimed at reducing unintended pregnancies among childbearing women living with HIV. However, it is unclear whether this strategy has made any significant impact at the population level. This paper describes the prevalence and correlates of self-reported unplanned pregnancy among HIV-infected parturient women attending three large maternity centres in the Eastern Cape, South Africa. We also compare unplanned pregnancy rates between HIV-infected parturient women already in care (who have benefitted from services' integration) and newly diagnosed parturient women (who have not benefitted from services' integration). METHODS: Drawing from the baseline data of the East London Prospective Cohort Study (ELPCS), data of 594 parturient women living with HIV in the Eastern Cape were included. Chi-square statistics and binary logistics regression were employed to determine the correlates of unplanned pregnancy among the cohort. RESULTS: The prevalence of unplanned pregnancy was 71% (n = 422) with a higher rate among parturient women newly diagnosed during the index pregnancy (87%). Unplanned pregnancy was significantly associated with younger age, single status, HIV diagnosis at booking, high parity and previous abortion. Women who reported unplanned pregnancy were more likely to book late and have lower CD4 counts. After adjusting for confounding variables, having one child and five to seven children (AOR = 2.2; CI = 1.3-3.1), age less than 21 years (AOR = 3.3; CI = 1.1-9.8), late booking after 27 weeks (AOR = 2.7; CI = 1.5-5.0), not married (AOR = 4.3; CI = 2.7-6.8) and HIV diagnosis at booking (AOR = 3.0; CI = 1.6-5.8) were the significant correlates of unplanned pregnancy in the cohort. CONCLUSION: Unplanned pregnancy remains high overall among parturient women living with HIV in the region, however, with significant reduction among those who were exposed to integrated services. The study confirms that integration of HIV care and family planning services is an important strategy to reduce unplanned pregnancy among women living with HIV. The study's findings have significant implications for the elimination of mother-to-child transmission of HIV in South Africa. Innovative interventions are needed to further consolidate and maximise the benefit of the integration of family planning services with HIV care.

A New Class of Antibody-Drug Conjugates with Potent DNA Alkylating Activity.

The promise of tumor-selective delivery of cytotoxic agents in the form of antibody-drug conjugates (ADC) has now been realized, evidenced by the approval of two ADCs, both of which incorporate highly cytotoxic tubulin-interacting agents, for cancer therapy. An ongoing challenge remains in identifying potent agents with alternative mechanisms of cell killing that can provide ADCs with high therapeutic indices and favorable tolerability. Here, we describe the development of a new class of potent DNA alkylating agents that meets these objectives. Through chemical design, we changed the mechanism of action of our novel DNA cross-linking agent to a monofunctional DNA alkylator. This modification, coupled with linker optimization, generated ADCs that were well tolerated in mice and demonstrated robust antitumor activity in multiple tumor models at doses 1.5% to 3.5% of maximally tolerated levels. These properties underscore the considerable potential of these purpose-created, unique DNA-interacting conjugates for broadening the clinical application of ADC technology. Mol Cancer Ther; 15(8); 1870-8. ©2016 AACR.

ADME of antibody-maytansinoid conjugates.

The concept of treating cancer with antibody-drug conjugates (ADCs) has gained momentum with the favorable activity and safety of trastuzumab emtansine (T-DM1), SAR3419, and lorvotuzumab mertansine (IMGN901). All three ADCs utilize maytansinoid cell-killing agents which target tubulin and suppress microtubule dynamics. Each ADC utilizes a different optimized chemical linker to attach the maytansinoid to the antibody. Characterizing the absorption, distribution, metabolism, and excretion (ADME) of these ADCs in preclinical animal models is important to understanding their efficacy and safety profiles. The ADME properties of these ADCs in rodents were inferred from studies with radio-labeled ADCs prepared with nonbinding antibodies since T-DM1, SAR3419, IMGN901 all lack cross-reactivity with rodent antigens. For studies exploring tumor localization and activation in tumor-bearing mice, tritium-labeled T-DM1, SAR3419, and IMGN901 were utilized. The chemical nature of the linker was found to have a significant impact on the ADME properties of these ADCs-particularly on the plasma pharmacokinetics and observed catabolites in tumor and liver tissues. Despite these differences, T-DM1, SAR3419, and IMGN901 were all found to facilitate efficient deliveries of active maytansinoid catabolites to the tumor tissue in mouse xenograft models. In addition, all three ADCs were effectively detoxified during hepatobiliary elimination in rodents.

Supramolecular self-assembly on a solid support: metal-directed complementarity.

Resin immobilised (poly)-2,2'-bipyridines have been prepared and used as templates for the copper(II)-mediated assembly of alkene-functionalised 2,2'ratio6',2''-terpyridines which undergo subsequent templated metathesis to form complementary poly-2,2'ratio6',2''-terpyridine strands.

Alternative, age- and viral load-related routes of nelfinavir resistance in human immunodeficiency virus type 1-infected children receiving highly active antiretroviral therapy.

To assess prevalence of nelfinavir resistance mutations in children receiving highly active antiretroviral therapy, sequencing of protease gene from plasma of 53 human immunodeficiency virus-infected children was performed. The prevalence of L90M was similar to that of D30N. There was a significant correlation with a higher viral load and lower age and the occurrence of L90M. These findings suggest differential molecular age- and viral load-related routes for nelfinavir resistance.