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BACKGROUND: A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)-infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies. METHODS: We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals. RESULTS: From August 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele, and one of iniencephaly. In comparison, 15 neural-tube defects were found among 14,792 deliveries (0.10%) in which the mother was taking any non-dolutegravir ART at conception, 3 among 7959 (0.04%) in which the mother was taking efavirenz at conception, 1 among 3840 (0.03%) in which the mother started dolutegravir treatment during pregnancy, and 70 among 89,372 (0.08%) in HIV-uninfected mothers. The prevalence of neural-tube defects was higher in association with dolutegravir treatment at conception than with non-dolutegravir ART at conception (difference, 0.20 percentage points; 95% confidence interval [CI], 0.01 to 0.59) or with other types of ART exposure. Major external structural defects were found in 0.95% of deliveries among women exposed to dolutegravir at conception and 0.68% of those among women exposed to non-dolutegravir ART at conception (difference, 0.27 percentage points; 95% CI, -0.13 to 0.87). CONCLUSIONS: The prevalence of neural-tube defects was slightly higher in association with dolutegravir exposure at conception than with other types of ART exposure at conception (3 per 1000 deliveries vs. 1 per 1000 deliveries). (Funded by the National Institutes of Health.).
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Antirretrovirais/efeitos adversos , Anormalidades Congênitas/epidemiologia , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Defeitos do Tubo Neural/induzido quimicamente , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Botsuana/epidemiologia , Quimioterapia Combinada , Feminino , Feto/efeitos dos fármacos , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Recém-Nascido , Defeitos do Tubo Neural/epidemiologia , Oxazinas , Piperazinas , Vigilância da População , Gravidez , Prevalência , Piridonas , Fatores SocioeconômicosRESUMO
Importance: Direct-acting antivirals (DAAs) are safe and highly effective for curing hepatitis C virus (HCV) infection, but their high cost led certain state Medicaid programs to impose coverage restrictions. Since 2015, many of these restrictions have been lifted voluntarily in response to advocacy or because of litigation. Objective: To estimate how the prescribing of DAAs to Medicaid patients changed after states eased access restrictions. Design, Setting, and Participants: This modified difference-in-differences analysis of 39 state Medicaid programs included Medicaid beneficiaries who were prescribed a DAA from January 1, 2015, to December 31, 2019. DAA coverage restrictions were measured based on a series of cross-sectional assessments performed from 2014 through 2022 by the US National Viral Hepatitis Roundtable and the Center for Health Law and Policy Innovation. Exposure: Calendar quarter when states eased or eliminated 3 types of DAA coverage restrictions: limiting treatment to patients with severe liver disease, restricting use among patients with active substance use, and requiring prescriptions to be written by or in consultation with specialists. States with none of these restrictions at baseline were excluded. Main Outcomes and Measures: Quarterly number of HCV DAA treatment courses per 100â¯000 Medicaid beneficiaries. Results: Of 39 states, 7 (18%) eliminated coverage restrictions, 25 (64%) eased restrictions, and 7 (18%) maintained the same restrictions from 2015 to 2019. During this period, the average quarterly use of DAAs increased from 669 to 3601 treatment courses per 100â¯000 Medicaid beneficiaries. After states eased or eliminated restrictions, the use of DAAs increased by 966 (95% CI, 409-1523) treatment courses per 100â¯000 Medicaid beneficiaries each quarter compared with states that did not ease or eliminate restrictions. Conclusions and Relevance: The results of this study suggest that there was greater use of DAAs after states relaxed coverage restrictions related to liver disease severity, sobriety, or prescriber specialty. Further reductions or elimination of these rules may improve access to a highly effective public health intervention for patients with HCV.
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Hepatite C Crônica , Hepatite C , Estados Unidos/epidemiologia , Humanos , Antivirais/uso terapêutico , Hepacivirus , Medicaid , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Estudos Transversais , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/induzido quimicamenteRESUMO
Igf2 mRNA binding protein 1 (IMP1, CRD-BP, ZBP-1) is a messenger RNA binding protein that we have shown previously to regulate colorectal cancer (CRC) cell growth in vitro. Furthermore, increased IMP1 expression correlates with enhanced metastasis and poor prognosis in CRC patients. In the current study, we sought to elucidate IMP1-mediated functions in CRC pathogenesis in vivo. Using CRC cell xenografts, we demonstrate that IMP1 overexpression promotes xenograft tumor growth and dissemination into the blood. Furthermore, intestine-specific knockdown of Imp1 dramatically reduces tumor number in the Apc (Min/+) mouse model of intestinal tumorigenesis. In addition, IMP1 knockdown xenografts exhibit a reduced number of tumor cells entering the circulation, suggesting that IMP1 may directly modulate this early metastatic event. We further demonstrate that IMP1 overexpression decreases E-cadherin expression, promotes survival of single tumor cell-derived colonospheres and promotes enrichment and maintenance of a population of CD24+CD44+ cells, signifying that IMP1 overexpressing cells display evidence of loss of epithelial identity and enhancement of a tumor-initiating cell phenotype. Taken together, these findings implicate IMP1 as a modulator of tumor growth and provide evidence for a novel role of IMP1 in early events in CRC metastasis.
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Proteína da Polipose Adenomatosa do Colo/fisiologia , Transformação Celular Neoplásica/patologia , Neoplasias Colorretais/patologia , Intestinos/patologia , Células-Tronco Neoplásicas/patologia , Proteínas de Ligação a RNA/fisiologia , Animais , Apoptose , Western Blotting , Adesão Celular , Diferenciação Celular , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/metabolismo , Embrião de Mamíferos/metabolismo , Embrião de Mamíferos/patologia , Transição Epitelial-Mesenquimal , Fibroblastos/metabolismo , Fibroblastos/patologia , Xenoenxertos , Humanos , Técnicas Imunoenzimáticas , Integrases/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Nus , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Células-Tronco Neoplásicas/metabolismo , Fenótipo , Células Tumorais CultivadasRESUMO
Patients receiving chimeric antigen receptor T cell (CAR-T) therapy may have impaired humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations owing to their underlying hematologic malignancy, prior lines of therapy, and CAR-T-associated hypogammaglobulinemia. Comprehensive data on vaccine immunogenicity in this patient population are limited. A single-center retrospective study of adults receiving CD19 or BCMA-directed CAR-T therapy for B cell non-Hodgkin lymphoma or multiple myeloma was conducted. Patients received at least 2 doses of SARS-CoV-2 vaccination with BNT162b2 or mRNA-1273 or 1 dose of Ad26.COV2.S and had SARS-CoV-2 anti-spike antibody (anti-S IgG) levels measured at least 1 month after the last vaccine dose. Patients were excluded if they received SARS-CoV-2 monoclonal antibody therapy or immunoglobulin within 3 months of the index anti-S titer. The seropositivity rate (assessed by an anti-S assay cutoff of ≥.8 U/mL in the Roche assay) and median anti-S IgG titers were analyzed. Fifty patients were included in the study. The median age was 65 years (interquartile range [IQR], 58 to 70 years), and the majority were male (68%). Thirty-two participants (64%) had a positive antibody response, with a median titer of 138.5 U/mL (IQR, 11.61 to 2541 U/mL). Receipt of ≥3 vaccines was associated with a significantly higher anti-S IgG level. Our study supports current guidelines for SARS-CoV-2 vaccination among recipients of CAR-T therapy and demonstrates that a 3-dose primary series followed by a fourth booster increases antibody levels. However, the relatively low magnitude of titers and low percentage of nonresponders demonstrates that further studies are needed to optimize vaccination timing and determine predictors of vaccine response in this population.
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COVID-19 , Receptores de Antígenos Quiméricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ad26COVS1 , Anticorpos Antivirais , Vacina BNT162 , Terapia Baseada em Transplante de Células e Tecidos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Imunogenicidade da Vacina , Imunoglobulina G , Receptores de Antígenos Quiméricos/uso terapêutico , Estudos Retrospectivos , SARS-CoV-2RESUMO
PURPOSE: Timely radiation treatment (RT) is critical in cervical cancer treatment, but patients in low- and middle-income countries (LMICs) in sub-Saharan Africa often face barriers that delay care. Time to care was benchmarked in a multidisciplinary team (MDT) setting in Botswana. METHODS: Time intervals between steps in care were recorded for 230 patients reviewed at MDT between January 2016 and July 2018. Associations between RT delay and overall survival (OS) were evaluated using Kaplan-Meier curves and multivariable Cox proportional hazards models. RESULTS: For patients who received RT (n = 187; 81.3%), the median biopsy to pathology reporting interval was 25 (IQR, 19-36) days and was 57 (IQR, 28-68) days for patients who did not (P = .003). Intervals in care did not differ between patients who did and did not receive RT. Among treated patients, the uppermost quartile interval from pathology reporting to RT initiation was ≥111 days and that from RT simulation to initiation was ≥12 days. Among patients receiving a RT dose of ≥65 Gy (n = 100), the delay from RT simulation to initiation of >12 days was associated with worse median OS (2.0 v 4.6 years; P = .048); this association trended toward, although did not meet, statistical significance on multivariable analysis (hazard ratio, 2.35; 95% CI, 0.95 to 5.85; P = .07). CONCLUSION: The MDT-coordinated care model allows for systematic benchmarking of the patient treatment cascade. Barriers to timely treatment exist for this cohort in Botswana, and RT delay may be associated with OS of patients receiving curative treatment. Interventions to accelerate the timing of the radiation oncology care cascade may improve clinical outcomes in this LMIC setting.
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Radioterapia (Especialidade) , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/radioterapia , Benchmarking , Biópsia , BotsuanaRESUMO
Background: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), several variables may impact the humoral response among patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A retrospective chart review was conducted among SARS-CoV-2-vaccinated HSCT recipients between 2020 and 2022 at a single center in Boston, Massachusetts. Patients age ≥18 years who received doses of Pfizer, Moderna, or J&J vaccines were included. Anti-spike (S) immunoglobulin G (IgG) titer levels were measured using the Roche assay. Responders (≥0.8â U/mL) and nonresponders (<0.8â U/mL) were categorized and analyzed. Multivariable linear and logistic regression were used to estimate the correlation coefficient and odds ratio of response magnitude and status. Results: Of 152 HSCT recipients, 141 (92.8%) were responders, with a median (interquartile range [IQR]) anti-S IgG titer of 2500 (107.9-2500) U/mL at a median (IQR) of 80.5 (36-153.5) days from last dose, regardless of the number of doses received. Higher quantitative titers were associated with receipt of more vaccine doses (coeff, 205.79; 95% CI, 30.10 to 381.47; P = .022), being female (coeff, 343.5; 95% CI, -682.6 to -4.4; P = .047), being younger (<65 years; coeff, 365.2; 95% CI, -711.3 to 19.1; P = .039), and not being on anti-CD20 therapy (coeff, -1163.7; 95% CI, -1717.7 to -609.7; P = .001). Being male (odds ratio [OR], 0.11; 95% CI, 0.01 to 0.93; P = .04) and being on anti-CD20 therapy (OR, 0.16; 95% CI, 0.03 to 0.70; P = .016) were associated with nonresponse. Conclusions: Overall, most HSCT recipients had high SARS-CoV-2 antibody responses. More vaccine doses improved the magnitude of immune responses. Anti-S IgG monitoring may be useful for identifying attenuated vaccine-induced responses.
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Infecções por Clostridium/epidemiologia , Fármacos Gastrointestinais/uso terapêutico , Lactulose/uso terapêutico , Cirrose Hepática/complicações , Idoso , Estudos de Casos e Controles , Infecções por Clostridium/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrebióticosRESUMO
This cohort study examines the alignment of vaccination and SARS-CoV-2 risk in Massachusetts by creating and applying a vaccination-to-infection risk ratio.
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COVID-19 , Anticorpos Antivirais , COVID-19/epidemiologia , Vacinas contra COVID-19 , Estudos de Coortes , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , VacinaçãoRESUMO
OBJECTIVE: Cancer drug stockouts occur at high frequencies globally, however, their effects on treatment are understudied in sub-Saharan Africa (SSA). We aimed to determine whether causes of suboptimal cancer treatment prescriptions differed between periods of stockout and full treatment supply. DESIGN: A retrospective cohort study of systemic therapy prescriptions for patients diagnosed with the twelve most common solid tumour cancers treated in 2016. SETTING: Princess Marina Hospital in Gaborone, Botswana. PARTICIPANTS: Patients in the retrospective cohort who experienced any suboptimal treatment events, defined as ≥7 days delay or switch from guideline-concordant initiated therapy. PRIMARY AND SECONDARY OUTCOME MEASURES: Frequency of delays and patterns of prescription changes for specific regimens and cancer types. RESULTS: 167/378 patients contributed to 320 suboptimal events (115 therapy switches, 167 delays and 38 events with both), over 1452 total chemotherapy cycles received. Events during stockout were 43% delays, 43% switches and 14% both during stockout periods and 67.2% delays, 24.4% switches and 8.4% both during non-stockout periods (p<0.001). Majority of switches involved de-escalation of initially prescribed guideline-recommended regimens in patients with breast cancer, Kaposi sarcoma and patients with colorectal cancer, which occurred more frequently during periods of drug stockouts. Among patients with breast cancer, substitution of docetaxel for paclitaxel event occurred exclusively during paclitaxel drug stockout. Delays of ≥7 days events were most frequent in breast cancer patients receiving paclitaxel during stockout, and combination doxorubicin and cyclophosphamide even during periods of non-stockout. CONCLUSIONS: The aetiology of suboptimal events differed during stockout and non-stockout periods. Prescription patterns that involved de-escalation of initiated therapy and substitution of paclitaxel with docetaxel occurred frequently during periods of drug stockout. Further research needs to be conducted to understand the impact of stockout on survival and barriers to maintaining essential cancer medicines supplies in SSA, and the factors driving frequent delays in therapy delivery.
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Neoplasias da Mama , Preparações Farmacêuticas , Protocolos de Quimioterapia Combinada Antineoplásica , Botsuana , Neoplasias da Mama/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Prescrições , Estudos RetrospectivosRESUMO
BACKGROUND: Vaginal discharge syndrome (VDS) is a common clinical diagnosis during pregnancy in Botswana; it is treated with broad-spectrum antibiotics using a syndromic approach. We evaluated associations between the syndromic management of VDS and adverse birth outcomes. METHODS: The Tsepamo Study performs birth outcomes surveillance at government hospitals throughout Botswana. Obstetric record data collected from August 2014 to March 2019 were analyzed. Chi-square tests were conducted to compare proportions of maternal characteristics and infant outcomes. To avoid immortal time bias, all analyses were conducted among women who presented to care before 24 weeks gestation, with VDS categorized as present or absent by 24 weeks gestation. Log-binomial regression models were generated to determine associations between treated VDS and infant outcomes. RESULTS: VDS was diagnosed in 36 731 (30.7%) pregnant women, of whom 33 328 (90.7%) received antibiotics. Adjusted analyses yielded a harmful association between treated VDS and very preterm delivery (adjusted risk ratio,â 1.11; 95% CI, 1.02-1.21). This association remained when restricting to women with VDS who received the recommended antibiotic treatment regimen. Sensitivity analyses produced nonsignificant associations when women with treated VDS were compared with women without VDS who received antibiotics for other indications. CONCLUSIONS: A clinical diagnosis of VDS is common among pregnant women in Botswana, and the majority receive antibiotics in pregnancy. Although analyses of VDS occurring later in pregnancy are precluded by immortal time bias, a modest association between treated VDS and very preterm delivery was observed among women diagnosed with VDS by 24 weeks gestation.
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OBJECTIVES: This study aims to evaluate the prevalence and outcome of twin pregnancies in Botswana. SETTING: The Tsepamo Study conducted birth outcomes surveillance at 8 government-run hospitals (~45% of all births in Botswana) from August 2014 to June 2018 and expanded to 18 hospitals (~70% of all births in Botswana) from July 2018 to March 2019. PARTICIPANTS: Data were collected for all live-born and stillborn in-hospital deliveries with a gestational age (GA) greater than 24 weeks. This analysis included 117 593 singleton and 3718 twin infants (1859 sets (1.6%)) born to 119 477 women between August 2014 and March 2019 and excluded 73 higher order multiples (23 sets of triplets and 1 set of quadruplets). OUTCOMES MEASURED: Our primary outcomes were preterm delivery (<37 weeks GA), very preterm delivery (<32 weeks GA) and stillbirth (APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score of 0, 0, 0). RESULTS: Women with twin pregnancies had a similar median number of antenatal care visits (9 vs 10), but were more likely to deliver in a tertiary centre (54.8% vs 45.1%, p<0.001) and more likely to have a cesarean-section (54.6% vs 22.0%, p<0.001) than women with singletons. Compared with singletons, twin pregnancies had a higher risk of preterm delivery (<37 weeks GA) (47.6% vs 16.7%, adjusted risk ratio (aRR) 2.8, 95% CI 2.7 to 2.9) and very preterm delivery (<32 weeks) (11.8% vs 4.0%, aRR 3.0 95% CI 2.6 to 3.4). Among all twin pregnancies, 128 (6.9%) had at least one stillborn infant compared with 2845 (2.4%) stillbirths among singletons (aRR 2.8, 95% CI 2.3 to 3.3). CONCLUSION: Adverse birth outcomes are common among twins in Botswana, and are often severe. Interventions that allow for earlier identification of twin gestation and improved antenatal management of twin pregnancies may improve infant and child survival.
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Gravidez de Gêmeos , Nascimento Prematuro , Botsuana/epidemiologia , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , PrevalênciaRESUMO
OBJECTIVE: Early deficiencies in testing capacity contributed to poor control of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the context of marked improvement in SARS-CoV-2 testing infrastructure, we sought to examine the alignment of testing with epidemic intensity to mitigate subsequent waves of COVID-19 in Massachusetts. METHODS: We compiled publicly available weekly SARS-CoV-2 molecular testing data for period (May 27 to October 14, 2020) following the initial COVID-19 wave. We defined testing intensity as weekly SARS-CoV-2 tests performed per 100,000 population and used weekly test positivity (percent of tests positive) as a measure of epidemic intensity. We considered optimal alignment of testing resources to be matching community ranks of testing and positivity. In communities with a lower rank of testing than positivity in a given week, the testing gap was calculated as the additional tests required to achieve matching ranks. Multivariable Poisson modeling was utilized to assess for trends and association with community characteristics. RESULTS: During the observation period, 4,262,000 tests were reported in Massachusetts and the misalignment of testing with epidemic intensity increased. The weekly testing gap increased 9.0% per week (adjusted rate ratio [aRR]: 1.090, 95% confidence interval [CI]: 1.08-1.10). Increasing levels of community socioeconomic vulnerability (aRR: 1.35 per quartile increase, 95% CI: 1.23-1.50) and the highest quartile of minority and language vulnerability (aRR: 1.46, 95% CI 0.96-1.49) were associated with increased testing gaps, but the latter association was not statistically significant. Presence of large university student population (>10% of population) was associated with a marked decrease in testing gap (aRR 0.21, 95% CI: 0.12-0.38). CONCLUSION: These analyses indicate that despite objectives to promote equity and enhance epidemic control in vulnerable communities, testing resources across Massachusetts have been disproportionally allocated to more affluent communities. Worsening structural inequities in access to SARS-CoV-2 testing increase the risk for another intense wave of COVID-19 in Massachusetts, particularly among vulnerable communities.
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BACKGROUND: Recent data suggests clinically significant weight gain among non-pregnant HIV-positive adults after starting dolutegravir-based ART (DTG). Excess or insufficient weight gain in pregnancy could adversely impact pregnancy outcomes, but data for pregnant women receiving DTG are limited. METHODS: The Tsepamo Study captured data at delivery sites in Botswana from 2014 to 2019. HIV testing, HIV treatment information, and weight measurements during antenatal care were abstracted from the maternity obstetric record at delivery. HIV-positive women initiating DTG or efavirenz-based ART (EFV) between conception and 17 weeks gestation and HIV-uninfected women first presenting for antenatal care before 17 weeks gestation were included. We evaluated weekly weight gain, total 18-week weight gain, excess weight gain (>0.59 kg/week), insufficient weight gain (<0.18 kg/week), and weight loss between 18±2 and 36±2 weeks gestation, adjusting for demographic and clinical variables. FINDINGS: Baseline characteristics were similar by exposure group, including pre-pregnancy and early pregnancy weight. Compared with EFV, mean weekly weight gain between 18 and 36 weeks gestation was 0.05 (95% CI 0.03, 0.07) kg/week higher for women initiating DTG and 0.12 (0.10, 0.14) kg/week higher for HIV-uninfected women. Mean 18-week weight gain was 1.05 (95% CI 0.61, 1.49) kg higher for women initiating DTG and 2.31 (1.85, 2.77) kg higher for HIV-uninfected women, compared with EFV. Women initiating DTG were more likely to gain excess weight but less likely to gain insufficient weight or lose weight than women initiating EFV. INTERPRETATION: Women initiating DTG compared with EFV during pregnancy gained more weight between 18 and 36 weeks gestation. Neither group gained as much weight as HIV-uninfected women. Initiating DTG compared with EFV during pregnancy could increase the risk of excess weight gain but decrease the risk of insufficient weight gain and weight loss, which could have positive and negative consequences in pregnancy. Our findings are consistent with prior studies in non-pregnant adults.
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BACKGROUND: In Botswana, nearly two-thirds of cervical cancer patients are HIV-positive. This study examined the relationship between CD4 count and chemoradiation therapy outcomes among cervical cancer patients with HIV. SETTING: A prospective cohort study of 231 HIV-positive women with locally invasive cervical cancer was conducted in Gaborone, Botswana from January 2015 to February 2018. METHODS: Primary outcome was survival, defined as time from scheduled end of chemoradiation therapy to death or last contact with patient. Nadir CD4 count was defined as lowest CD4 available before cancer diagnosis. Delta CD4 count was defined as improvement from nadir CD4 to CD4 at cancer diagnosis. Hazard ratio (HR) analyses were adjusted for presenting variables (age, baseline hemoglobin, cancer stage, and performance status) and treatment variables (chemotherapy cycles and radiation dose). RESULTS: Two hundred thirty-one patients were included in nadir CD4 analysis; 139 were included in delta CD4 analysis. Higher delta CD4 was significantly associated with reduced mortality after adjusting for presenting and treatment variables (CD4 100-249: HR 0.45, 95% CI: 0.21 to 0.95; CD4 ≥250: HR 0.45, 95% CI: 0.20 to 1.02). Higher nadir CD4 showed a trend toward reduced mortality after adjusting for presenting and treatment variables (HR 0.94, 95% CI: 0.84 to 1.06). CONCLUSIONS: Higher delta CD4 (greater improvement from nadir CD4 to CD4 at cervical cancer diagnosis) is significantly associated with lower mortality. Although not statistically significant, data suggest that higher nadir CD4 may reduce mortality. These results reinforce the importance of early HIV diagnosis and antiretroviral therapy initiation, as their effects influence cervical cancer outcomes years later.
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Contagem de Linfócito CD4/métodos , Quimiorradioterapia/métodos , Infecções por HIV/complicações , Neoplasias do Colo do Útero/terapia , Adulto , Fármacos Anti-HIV/uso terapêutico , Botsuana , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
BACKGROUND: A large-scale evaluation of mother-to-child transmission (MTCT) with dolutegravir (DTG)-based antiretroviral treatment (ART) has not been conducted previously. SETTING: Botswana was the first African country to change from efavirenz (EFV)/tenofovir (TDF)/emtricitabine (FTC) to DTG/TDF/FTC first-line ART. METHODS: From April 2015 to July 2018, the Early Infant Treatment Study offered HIV DNA testing at <96 hours of life. Maternal ART regimen was available for screened infants who could be linked to the separate Tsepamo surveillance study database. We evaluated characteristics of HIV-positive infants, and compared MTCT rates by ART regimen for linked infants. RESULTS: Of 10,622 HIV-exposed infants screened, 42 (0.40%) were HIV-positive. In total, 5064 screened infants could be linked to the surveillance database, including 1235 (24.4%) exposed to DTG/TDF/FTC and 2411 (47.6%) exposed to EFV/TDF/FTC. MTCT was rare when either regimen was started before conception: 0/213 [0.00%, 95% confidence interval (CI): 0.00% to 1.72%] on DTG, 1/1497 (0.07%, 95% CI: 0.00% to 0.37%) on EFV. MTCT was similar for women starting each ART regimen in pregnancy: 8/999 (0.80%, 95% CI: 0.35% to 1.57%) for DTG and 8/883 (0.91%, 95% CI: 0.39% to 1.78%) for EFV (risk difference 0.11%, 95% CI: -0.79% to 1.06%). Most MTCT events (4/8 with DTG, 6/9 with EFV) occurred when ART was started <90 days before delivery. Infants exposed to DTG in utero had lower baseline HIV RNA compared with other HIV-infected infants. CONCLUSION: In utero MTCT in Botswana remains rare in the DTG era. No significant MTCT differences were observed between DTG/TDF/FTC and EFV/TDF/FTC. Risk was highest for both groups when ART was started in the third trimester.
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Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Alcinos/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Botsuana , Ciclopropanos/uso terapêutico , Indutores do Citocromo P-450 CYP2B6/uso terapêutico , Inibidores do Citocromo P-450 CYP2C19/uso terapêutico , Inibidores do Citocromo P-450 CYP2C9/uso terapêutico , Indutores do Citocromo P-450 CYP3A/uso terapêutico , Combinação de Medicamentos , Emtricitabina/uso terapêutico , Feminino , Humanos , Mães , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Gravidez , Piridonas/uso terapêutico , Fatores de Risco , Tenofovir/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Although musculoskeletal injuries have increased in sub-Saharan Africa, data on the economic burden of non-fatal musculoskeletal injuries in this region are scarce. OBJECTIVE: Socioeconomic costs of orthopedic injuries were estimated by examining both the direct hospital cost of orthopedic care as well as indirect costs of orthopedic trauma using disability days and loss of work as proxies. METHODS: This study surveyed 200 patients seen in the outpatient orthopedic ward of the Kilimanjaro Christian Medical Center, a tertiary hospital in Northeastern Tanzania, during the month of July 2016. FINDINGS: Of the patients surveyed, 88.8% earn a monthly income of less than $250 and the majority of patients (73.7%) reported that the healthcare costs of their musculoskeletal injuries were a catastrophic burden to them and their family with 75.0% of patients reporting their medical costs exceeded their monthly income. The majority (75.3%) of patients lost more than 30 days of activities of daily living due to their injury, with a median (IQR) functional day loss of 90 (30). Post-injury disability led to 40.6% of patients losing their job and 86.7% of disabled patients reported a wage decrease post-injury. There were significant associations between disability and post-injury unemployment (p < .0001) as well as lower post-injury wages (p = .022). CONCLUSION: This exploratory study demonstrates that in this region of the world, access to definitive treatment post-musculoskeletal injury is limited and patients often suffer prolonged disabilities resulting in decreased employment and income.
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Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Doenças Musculoesqueléticas/economia , Ortopedia , Ferimentos e Lesões/economia , Atividades Cotidianas , Adolescente , Adulto , Idoso , Assistência Ambulatorial/economia , Traumatismos do Braço/economia , Traumatismos do Braço/terapia , Criança , Pré-Escolar , Pessoas com Deficiência , Emprego/economia , Feminino , Lesões do Quadril/economia , Lesões do Quadril/terapia , Humanos , Renda , Lactente , Recém-Nascido , Traumatismos da Perna/economia , Traumatismos da Perna/terapia , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/economia , Traumatismo Múltiplo/terapia , Doenças Musculoesqueléticas/terapia , Lesões do Pescoço/economia , Lesões do Pescoço/terapia , Procedimentos Ortopédicos/economia , Estudos Prospectivos , Salários e Benefícios/economia , Traumatismos da Coluna Vertebral/economia , Traumatismos da Coluna Vertebral/terapia , Tanzânia , Ferimentos e Lesões/terapia , Adulto JovemRESUMO
PURPOSE: Low- and middle-income countries account for 86% of all cervical cancer cases and 88% of cervical cancer mortality globally. Successful management of cervical cancer requires resources that are scarce in sub-Saharan Africa, especially in rural settings. Here, we describe the early clinical outcomes and implementation lessons learned from the Rwanda Ministry of Health's first national cancer referral center, the Butaro Cancer Center of Excellence (BCCOE). We hypothesize that those patients presenting at earlier stage and receiving treatment will have higher rates of being alive. METHODS: The implementation of cervical cancer services included developing partnerships, clinical protocols, pathology services, and tools for monitoring and evaluation. We conducted a retrospective study of patients with cervical cancer who presented at BCCOE between July 1, 2012, and June 30, 2015. Data were collected from the electronic medical record system and by manually reviewing medical records. Descriptive, bivariable and multivariable statistical analyses were conducted to describe patient demographics, disease profiles, treatment, and clinical outcomes. RESULTS: In all, 373 patients met the study inclusion criteria. The median age was 53 years (interquartile rage, 45 to 60 years), and 98% were residents of Rwanda. Eighty-nine percent of patients had a documented disease stage: 3% were stage I, 48% were stage II, 29% were stage III, and 8% were stage IV at presentation. Fifty percent of patients were planned to be treated with a curative intent, and 54% were referred to chemoradiotherapy in Uganda. Forty percent of patients who received chemoradiotherapy were in remission. Overall, 25% were lost to follow-up. CONCLUSION: BCCOE illustrates the feasibility and challenges of implementing effective cervical cancer treatment services in a rural setting in a low-income country.
Assuntos
Neoplasias do Colo do Útero/terapia , Feminino , Humanos , Pessoa de Meia-Idade , RuandaRESUMO
This study examined hip fractures during a 5-year period at Kilimanjaro Christian Medical Center (KCMC). There was a general increase in proportions of fragility hip fractures during this period. PURPOSE: Fragility hip fractures are expected to increase in low-resource countries. This study examined hip fractures in the osteoporotic age group during a 5-year period at the Kilimanjaro Christian Medical Center (KCMC), which is located in Moshi, Tanzania. METHODS: We conducted a retrospective study of all hip fracture patients above the age of 50 who were admitted to KCMC between January 1, 2011 and December 31, 2015. Objective measures including patient demographics, mechanism of injury, and X-ray evaluation were used to differentiate high- and low-energy fractures. Low-energy hip fractures with no other suspected pathological processes on X-ray were labelled as fragility fractures. RESULTS: Three hundred forty patients were admitted in the study period and 222 patients met the inclusion criteria. Males contributed to 59.5% of hip fractures. Falls from standing height constituted the majority of fractures (76%) followed by injury from road traffic crashes (14%). Regardless of high- or low-energy aetiology, intertrochanteric fracture dominated representing 54.5% of all hip fractures. 75.6% (n = 168) of the analysed patients had fragility fractures. The fragility fractures were 55.8% (n = 96) intertrochanteric, 28.5% (n = 49) cervical, 9.9% (n = 17) subtrochanteric, and 5.8% (n = 10) mixed subtrochanteric with intertrochanteric. We noted a 2.34% per year increase in the proportions of fragility fractures among all included hip fractures over 5 years. CONCLUSION: We concluded that men and women contributed almost equally to the fragility hip fracture burden. The dominant cause of hip fractures overall was low-energy injuries. There was an increase in proportions of fragility hip fractures in the period of January 2011 to December 2015.
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Fraturas do Quadril/etiologia , Hospitalização/estatística & dados numéricos , Fraturas por Osteoporose/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Quadril/epidemiologia , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Encaminhamento e Consulta , Estudos Retrospectivos , Distribuição por Sexo , Tanzânia/epidemiologiaRESUMO
This paper discusses how the United States biopharmaceutical market has been affected by recent changes in patent law resulting from United States legislations (Biologics Price Competition and Innovation Act and the Leahy-Smith America Invents Act) and Supreme Court precedents (Mayo Collaborative Services v. Prometheus Laboratories, Inc. and Molecular Pathology v. Myriad Genetics). The authors interviewed eight key opinion leaders from the United States knowledgeable in biopharmaceuticals, including industry veterans, patent counsel, senior scientists and jurists. This paper summarizes the opinions of the key opinion leaders. This paper explains the impact of these Supreme Court decisions - i.e., broadening the exceptions to patent eligibility for law of nature and natural phenomenon - on biopharmaceutical innovations and provides future perspectives.