Beyond too little, too late and too much, too soon: a pathway towards evidence-based, respectful maternity care worldwide.

On the continuum of maternal health care, two extreme situations exist: too little, too late (TLTL) and too much, too soon (TMTS). TLTL describes care with inadequate resources, below evidence-based standards, or care withheld or unavailable until too late to help. TLTL is an underlying problem associated with high maternal mortality and morbidity. TMTS describes the routine over-medicalisation of normal pregnancy and birth. TMTS includes unnecessary use of non-evidence-based interventions, as well as use of interventions that can be life saving when used appropriately, but harmful when applied routinely or overused. As facility births increase, so does the recognition that TMTS causes harm and increases health costs, and often concentrates disrespect and abuse. Although TMTS is typically ascribed to high-income countries and TLTL to low-income and middle-income ones, social and health inequities mean these extremes coexist in many countries. A global approach to quality and equitable maternal health, supporting the implementation of respectful, evidence-based care for all, is urgently needed. We present a systematic review of evidence-based clinical practice guidelines for routine antenatal, intrapartum, and postnatal care, categorising them as recommended, recommended only for clinical indications, and not recommended. We also present prevalence data from middle-income countries for specific clinical practices, which demonstrate TLTL and increasing TMTS. Health-care providers and health systems need to ensure that all women receive high-quality, evidence-based, equitable and respectful care. The right amount of care needs to be offered at the right time, and delivered in a manner that respects, protects, and promotes human rights.

Evolution of antiretroviral therapy services for HIV-infected pregnant women in Cape Town, South Africa.

BACKGROUND: Approaches to antiretroviral therapy (ART) in HIV-infected pregnant women have changed considerably in recent years, but there are few comparative data on the implementation of different models of service delivery. METHODS: Using routine clinic records we examined ART initiation in pregnant women attending a large antenatal care (ANC) facility between January 2010 and December 2013 in Cape Town, South Africa. Over this time six different service delivery models were implemented sequentially to provide ART in pregnancy, including the integration of ART into ANC, use of point-of-care CD4 cell count testing, and universal ART initiation for all HIV-infected pregnant women. RESULTS: During the study period 19,432 women sought ANC, levels of HIV testing were high (98%) and 30% of pregnant women tested HIV-positive. Integration of ART into ANC was associated with significant increases in the proportion of eligible women initiating treatment before delivery compared to referral to a separate ART clinic (p<0.001). When CD4 cell counts were used to determine ART eligibility, point-of-care testing was associated with decreased delays to ART initiation compared to laboratory-based testing (p<0.001). The strategy of universal ART led to the highest levels of ART initiation (with 92% of women starting before delivery) and the shortest delays, with 82% of women starting ART on the day of the first ANC visit. CONCLUSION: Developments in service delivery models, most notably service integration and universal ART for pregnant women, have improved antenatal ART initiation dramatically in this setting. Further research is needed into how strategies for antenatal ART initiation impact maternal and child health over the long-term.

The Columbia-Harlem Homeless Medical Partnership: a new model for learning in the service of those in medical need.

Though altruism and patient advocacy are promoted in medical education curricula, students are given few opportunities to develop these skills. Student-run clinics focusing on the health needs of the underserved can provide important health services to needy patients while providing students with career-influencing primary care experiences. The Columbia-Harlem Homeless Medical Partnership (CHHMP)-a project initiated by medical students to provide primary care to Northern Manhattan's homeless population-serves as a new model of service learning in medical education. Unlike many other student-run clinics, CHHMP has developed direct patient outreach, continuous care (stable "student-patient teams" and a weekly commitment for all volunteers), and regular internal data review. Chart review data presented demonstrate the project's success in providing care to the clinic's target population of homeless and unstably housed patients. Targeted outreach efforts among clients have increased rates of patient follow-up at each subsequent review period. Additionally, CHHMP has used review data to develop services concordant with identified patient needs (psychiatric care and social services). CHHMP has recruited a committed group of volunteers and continues to engender an interest in the health needs of the underserved among students. Not only does CHHMP provide a "medical home" for homeless patients, it also provides a space in which students can develop skills unaddressed in large teaching hospitals. This project, a "win-win" for patients and students, serves as a unique model for community health-based service learning in medical education.

Mechanisms of gastrointestinal CD4+ T-cell depletion during acute and early human immunodeficiency virus type 1 infection.

During acute and early human immunodeficiency virus type 1 (HIV-1) infection (AEI) more than 50% of CD4+ T cells are preferentially depleted from the gastrointestinal (GI) lamina propria. To better understand the underlying mechanisms, we studied virological and immunological events within the peripheral blood (PB) and GI tract during AEI. A total of 32 AEI subjects and 18 uninfected controls underwent colonic biopsy. HIV-1 viral DNA and RNA levels were quantified in CD4+ T cells derived from the GI tract and PB by using real-time PCR. The phenotype of infected cells was characterized by using combinations of immunohistochemistry and in situ hybridization. Markers of immunological memory, activation, and proliferation were examined by flow cytometry and immunohistochemistry, and the host-derived cytotoxic cellular response was examined by using immunohistochemistry. GI CD4+ T cells harbored, on average, 13-fold higher HIV-1 viral DNA levels and 10-fold higher HIV-1 RNA levels than PB CD4+ T cells during AEI. HIV-1 RNA was detected in both "activated" and "nonactivated" mucosal CD4+ T cells. A significantly higher number of activated and proliferating T cells were detected in the GI tract compared to the PB, and a robust cytotoxic response (HIV-1 specificity not determined) was detected in the GI tract as early as 18 days postinfection. Mucosal CD4+ T-cell depletion is multifactorial. Direct viral infection likely accounts for the earliest loss of CD4+ T cells. Subsequently, ongoing infection of susceptible CD4+ T cells, along with activation-induced cellular death and host cytotoxic cellular response, are responsible for the persistence of the lesion.

Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection.

BACKGROUND: During acute and early HIV-1 infection (AEI), up to 60% of CD4(+) T cells in the lamina propria of the lower gastrointestinal (GI) tract are lost as early as 2-4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART) is well established. However, the extent of immune reconstitution in the GI tract is unknown. METHODS AND FINDINGS: Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1-7 y of uninterrupted therapy). Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%-60% depletion of lamina propria lymphocytes despite 1-7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO+ HLA-DR+, returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4+ T cell depletion despite therapy. Rare HIV-1 RNA-expressing cells were detected by in situ hybridization. CONCLUSIONS: Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T cell homing to the GI tract. Although clinically silent over the short term, the long-term consequences of the persistence of this lesion may emerge as the HIV-1-infected population survives longer owing to the benefits of HAART.