Effectiveness of a provider and patient-focused intervention to improve hypertension management and control in the primary health care setting in Cuba: a controlled before-after study.

BACKGROUND: Implementation research to improve hypertension control is scarce in Latin America. We assessed the effectiveness of an intervention aimed at primary care practitioners and hypertensive patients in a setting that provides integrated care through an accessible network of family practices. METHODS: We conducted in Cardenas and Santiago, Cuba, a controlled before-after study in 122 family practices, which are staffed with a doctor and a nurse. The intervention comprised a control arm (usual care), an arm with a component targeting providers (hypertension management workshops), and an arm with, on top of the latter, a component targeting patients (hypertension schools). To evaluate the effect, we undertook a baseline survey before the intervention and an endline survey sixteen months after its start. In each survey, we randomly included 1400 hypertensive patients. Controlled hypertension, defined as a mean systolic and diastolic blood pressure below 140 and 90 mmHg, respectively, was the primary endpoint assessed. We performed linear and logistic regression with a Generalized Estimating Equations approach to determine if the proportion of patients with controlled hypertension changed following the intervention. RESULTS: Seventy-three doctors, including substitutes, and 54 nurses from the 61 intervention family practices attended the provider workshops, and 3308 patients -51.6% of the eligible ones- participated in the hypertension schools. Adherence to anti-hypertensive medication improved from 42% at baseline to 63% at the endline in the intervention arms. Under the provider intervention, the proportion of patients with controlled hypertension increased by 18.9%, from 48.7% at baseline to 67.6% at endline. However, adding the component that targeted hypertensive patients did not augment the effect. Compared to patients in the control arm, the adjusted OR of having controlled hypertension was 2.36 (95% CI, 1.73-3.22) in the provider and 2.00 (95% CI, 1.68-2.37) in the provider plus patient intervention arm. CONCLUSIONS: The intervention's patient component remains to be fine-tuned. Still, we demonstrate that it is feasible to substantially improve hypertension outcomes by intervention at the primary care level, despite an already relatively high control rate.

Protocol for a controlled before-after quasi-experimental study to evaluate the effectiveness of a multi-component intervention to reduce gaps in hypertension care and control in low-income communes of Medellin, Colombia.

INTRODUCTION: Research on public health interventions to improve hypertension care and control in low-income and middle-income countries remains scarce. This study aims to evaluate the effectiveness and assess the process and fidelity of implementation of a multi-component intervention to reduce the gaps in hypertension care and control at a population level in low-income communes of Medellin, Colombia. METHODS AND ANALYSIS: A multi-component intervention was designed based on international guidelines, cross-sectional population survey results and consultation with the community and institutional stakeholders. Three main intervention components integrate activities related to (1) health services redesign, (2) clinical staff training and (3) patient and community engagement. The effectiveness of the intervention will be evaluated in a controlled before-after quasi-experimental study, with two deprived communes of the city selected as intervention and control arms. We will conduct a baseline and an endline survey 2 years after the start of the intervention. The primary outcomes will be the gaps in hypertension diagnosis, treatment, follow-up and control. Effectiveness will be evaluated with the difference-in-difference measures. Generalised estimation equation models will be fitted considering the clustered nature of data and adjusting for potential confounding variables. The implementation process will be studied with mixed methods. Implementation fidelity will be documented to assess to which degree the intervention components were implemented as intended. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Research Committee of Metrosalud in Colombia (reference 1400/5.2), the Medical Ethics Committee of the Antwerp University Hospital (reference 18/40/424) and the Institutional Review Board of the Antwerp Institute of Tropical Medicine (reference 1294/19). We will share and discuss the study results with the community, institutional stakeholders and national health policymakers. We will publish them in national and international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05011838.

Intervención multicomponente para la reducción de las brechas en el proceso de atención y control de la hipertensión / Multicomponent Intervention to Reduce Gaps in the Hypertension Care and Control Process

RESUMEN Fundamento las evidencias sobre intervenciones de Salud Pública para mejorar las deficiencias en la atención y control de las personas hipertensas continúan siendo insuficientes. Objetivo implementar una intervención multicomponente para reducir dichas brechas en el Policlínico Julio Antonio Mella del municipio de Guanabacoa, evaluar el proceso de intervención, su efectividad y la fidelidad de su implementación. Método en relación a los resultados obtenidos en el estudio de base y recomendaciones técnicas nacionales e internacionales, se diseñó una intervención multicomponente que contará con los siguientes componentes: reorganización de los servicios de salud, capacitación del personal de salud, empoderamiento de los pacientes y participación de la comunidad. La efectividad de la intervención se evaluará por medio de un estudio cuasi-experimental (antes y después). La intervención cubrirá el policlínico antes mencionado, los diez consultorios del estudio de base y la población atendida por ellos. A los dos años de iniciada la implementación se aplicará nuevamente una encuesta poblacional y se estimará la diferencia en la magnitud de las brechas poblacionales pre-post intervención, además se monitoreará el proceso y se evaluará la fidelidad de la implementación de la intervención. Resultados reducir las brechas existentes en el proceso de atención al paciente hipertenso, identificar su magnitud en relación a la línea base. Conclusiones el estudio brindará evidencias al Ministerio de Salud Pública cubano y a otros países, especialmente de América Latina, para mejorar el cuidado del paciente con padecimientos crónicos.

ABSTRACT Background: the evidence on Public Health interventions to improve deficiencies in the care and control of hypertensive people continues to be insufficient. Objective: to implement a multicomponent intervention to reduce these gaps in the Julio Antonio Mella Polyclinic in the Guanabacoa municipality, to evaluate the intervention process, its effectiveness and the fidelity of its implementation. Method: in relation to the results obtained in the baseline study, national and international technical recommendations, a multicomponent intervention was designed that will have the following components: reorganization of health services, training of health personnel, empowerment of patients and community participation. The effectiveness of the intervention will be evaluated through a quasi-experimental study (before and after). The intervention will cover the aforementioned polyclinic, the ten baseline study clinics, and the population served by them. Two years after the start of implementation, a population survey will be applied again and the difference in the magnitude of the pre-post intervention population gaps will be estimated. In addition, the process will be monitored and the fidelity of the implementation of the intervention will be evaluated. Results: reduce existing gaps in the process of care for hypertensive patients, identify their magnitude in relation to the baseline. Conclusions: the study will provide evidence to the Cuban Ministry of Public Health and other countries, especially in Latin America, to improve the care of chronic patients.

Gaps in hypertension care and control: a population-based study in low-income urban Medellin, Colombia.

OBJECTIVES: To assess hypertension prevalence and the extent and associated factors of hypertension diagnosis, follow-up, treatment and control gaps in low-income urban Medellin, Colombia. METHODS: We randomly sampled 1873 adults aged 35 or older. Unaware hypertensive individuals were defined as those without previous diagnosis whose average blood pressure was equal to or above 140/90 mmHg. For aware hypertensive patients, control was delimited as average blood pressure below 140/90 if under 59 years old or diabetic, and as less than 150/90 otherwise. We used logistic regression to identify care gap-associated factors. RESULTS: Hypertension prevalence was 43.5% (95% CI 41.2-45.7). We found 28.2% aware and 15.3% unaware hypertensive individuals, which corresponds to a 35.1% (95% CI 31.9-38.5) underdiagnosis. This gap was determined by age, sex, education and lifestyle factors. 14.4% (95% CI 11.6-17.6) of aware hypertensive patients presented a follow-up gap, 93.4% (95% CI 90.9-95.2) were prescribed antihypertensive drugs, but 38.9% (95% CI 34.7-43.3) were not compliant. The latter was strongly associated with follow-up. The hypertension control gap in aware hypertensive patients, 39.0% (95% CI: 34.9-43.2), was associated with being older, having diabetes, weakly adhering to pharmacological treatment and receiving poor non-pharmacological advice. Overall, 60.4% (95% CI 57.0-63.8) of aware and unaware hypertensive participants had either diagnosed but uncontrolled or undiagnosed hypertension. CONCLUSIONS: We found high hypertension prevalence coupled with, from an international perspective, encouraging awareness and control figures. Still, there remains ample room for improvement. Our findings can assist in designing integrated primary healthcare measures that further strengthen equitable and effective access to hypertension care and control.

Out-of-pocket expenditure for hypertension care: a population-based study in low-income urban Medellin, Colombia.

Background Hypertension requires life-long medical care, which may cause economic burden and even lead to catastrophic health expenditure. Objective To estimate the extent of out-of-pocket expenditure for hypertension care at a population level and its impact on households' budgets in a low-income urban setting in Colombia. Methods We conducted a cross-sectional survey in Santa Cruz, a commune in the city of Medellin. In 410 randomly selected households with a hypertensive adult, we estimated annual basic household expenditure and hypertension-attributable out-of-pocket expenditure. For socioeconomic stratification, we categorised households according to basic expenditure quintiles. Catastrophic hypertension-attributable expenditure was defined as out-of-pocket expenditure above 10% of total household expenditure. Results The average annual basic household expenditure was US dollars at purchasing power parity (USD-PPP) $12,255.59. The average annual hypertension-attributable out-of-pocket expenditure was USD-PPP $147.75 (95% CI 120.93-174.52). It was incurred by 73.9% (95% CI 69.4%-78.1%) of patients, and consisted mainly of direct non-medical expenses (76.7%), predominantly for dietary requirements prescribed as non-pharmacological treatment and for transport to attend health care consultations. Medical out-of-pocket expenditure (23.3%) was for the most part incurred for pharmacological treatment. Hypertension-attributable out-of-pocket expenditure represented on average 1.6% (95% CI 1.3%-1.9%) of the total annual basic household expenditure. Eight households (2.0%; 95% CI 1.0%-3.8%) had catastrophic health expenditure; six of them belonged to the two lowest expenditure quintiles. Payments related to dietary requirements and transport to consultations were critical determinants of their catastrophic expenditure. Conclusions Out-of-pocket expenditure for hypertension care is moderate on average, but frequent, and mainly made up of direct non-medical expenses. Catastrophic health expenditure is uncommon and affects primarily households in the bottom socioeconomic quintiles. Financial protection should be strengthened by covering the costs of chronic diseases-related dietary requirements and transport to health services in the most deprived households. Abbreviations NCDs: Non-communicable diseases; LMICs: Low and middle-income countries; WHO: World Health Organization; HTN: hypertension; CVDs: Cardiovascular diseases; OOPE: out-of-pocket expenditure; USD-PPP: US dollars at purchasing power parity; CI: Confidence interval.

Contact evaluation and isoniazid preventive therapy among close and household contacts of tuberculosis patients in Lima, Peru: an analysis of routine data.

OBJECTIVE: Contacts of pulmonary tuberculosis (TB) cases are at high risk of TB infection and progression to disease. Close and household contacts and those <5 years old have the highest risk. Isoniazid preventive therapy (IPT) can largely prevent TB disease among infected individuals. International and Peruvian recommendations include TB contact investigation and IPT prescription to eligible contacts. We conducted a study in Lima, Peru, to determine the number of close and household contacts who were evaluated, started on IPT, and who completed it, and the factors associated to compliance with national guidelines. METHODS: We conducted a longitudinal retrospective study including all TB cases diagnosed between January 2015 and July 2016 in 13 health facilities in south Lima. Treatment cards, TB registers and clinical files were reviewed and data on index cases (sex, age, smear status, TB treatment outcome), contact investigation (sex, age, kinship to the index case, evaluations at month 0, 2 and 6) and health facility (number of TB cases notified per year, proportion of TB cases with treatment success) were extracted. We tabulated frequencies of contact evaluation by contact and index case characteristics. To investigate determinants of IPT initiation and completion, we used generalised linear mixed models. RESULTS: A total of 2323 contacts were reported by 662 index cases; the median number of contacts per case was four (IQR, 2-5). Evaluation at month 0 was completed by 99.2% (255/257) of contacts <5 and 98.1% (558/569) of contacts aged 5-19 years. Of 191 eligible contacts <5 years old, 70.2% (134) started IPT and 31.4% (42) completed it. Of 395 contacts 5-19 years old, 36.7% (145) started IPT and 32.4% (47) completed it. Factors associated to not starting IPT among contacts <5 years old were being a second-degree relative to the index case (OR 6.6 95CI% 2.6-16.5), not having received a tuberculin skin test (TST) (OR 3.9 95%CI 1.4-10.8), being contact of a smear-negative index case (OR 5.5 95%CI 2.0-15.1) and attending a low-caseload health facility (OR 2.8 95%CI 1.3-6.2). Factors associated to not starting IPT among 5-19 year-olds were age (OR 13.7 95%CI 5.9-32.0 for 16-19 vs. 5-7 years old), being a second-degree relative (OR 3.0 95%CI 1.6-5.6), not having received a TST (OR 5.4, 95%CI 2.5-11.8), being contact of a male index case (OR 2.1 95CI% 1.2-3.5), with smear-negative TB (OR 1.9 95%CI 1.0-3.6), and attending a high-caseload health facility (OR 2.1 95%CI 1.2-3.6). Factors associated to not completing IPT, among contacts who started, were not having received a TST (OR 3.4 95%CI 1.5-7.9 for <5 year-olds, and OR 4.3 95%CI 1.7-10.8 for those 5-19 years old), being contact of an index case with TB treatment outcome other than success (OR 9.3 95%CI 2.6-33.8 for <5 year-olds and OR 15.3 95%CI 1.9-125.8 for those 5-19 years old), and, only for those 5-19 years old, attending a health facility with high caseload (OR 3.2 95%CI 1.4-7.7) and a health facility with low proportion of TB cases with treatment success (OR 4.4 95%CI 1.9-10.2). CONCLUSIONS: We found partial compliance to TB contact investigation, and identified contact, index case and health facility-related factors associated to IPT start and completion that can guide the TB programme in increasing coverage and quality of this fundamental activity.

OBJECTIF: Les contacts des cas de tuberculose (TB) pulmonaire présentent un risque élevé d'infection à la TB et d'évolution vers la maladie. Les contacts étroits et familiaux et ceux de moins de 5 ans sont les plus à risque. Le traitement préventif à l'isoniazide (TPI) peut largement prévenir la maladie TB chez les personnes infectées. Nous avons mené une étude à Lima, au Pérou, pour déterminer le nombre de contacts proches et familiaux qui ont été évalués, qui ont commencé le TPI et qui l'ont achevé, ainsi que les facteurs associés au respect des directives nationales. MÉTHODES: Etude longitudinal rétrospective de tous les cas de TB diagnostiqués entre janvier 2015 et juillet 2016 dans 13 établissements de santé dans le sud de Lima. Les cartes de traitement, les registres de TB et les dossiers cliniques ont été examinés et des données sur les cas indice, l'investigation des contacts et les établissements de santé ont été extraites. Nous avons tabulé les fréquences d'évaluation des contacts par les caractéristiques des contacts et des cas indice. Pour étudier les déterminants de l'initiation et de l'achèvement du TPI, nous avons utilisé des modèles linéaires mixtes généralisés. RÉSULTATS: Au total, 2.323 contacts ont été rapportés par 662 cas indice; 70,2% des contacts âgés de moins de 5 ans ont commencé le TPI et 31,4% l'ont terminé, tandis que 36,7% des contacts âgés de 5 à 19 ans ont commencé le TPI et 32,4% l'ont terminé. Les facteurs associés au fait de ne pas commencer ou de terminer le TPI étaient: être un parent de second degré du cas indice, ne pas avoir reçu le test tuberculinique, être le contact d'un cas indice à frottis négatif et fréquenter un établissement de santé à faible charge de travail pour les moins de cinq ans contre fréquenter un établissement de santé à charge de travail élevée pour les contacts plus âgés. CONCLUSIONS: Nous avons constaté une compliance partielle à l'enquête sur les contacts de la TB, et avons identifié les facteurs liés aux contacts, aux cas indice et aux établissements de santé associés au début et à la fin du TPI qui peuvent guider le programme de TB dans l'augmentation de sa couverture et de sa qualité.

Severe post-kala-azar dermal leishmaniasis successfully treated with miltefosine in an Ethiopian HIV patient.

Post-kala-azar dermal leishmaniasis (PKDL) is a neglected tropical disease characterized by a dermatosis which often appears after successful treatment of visceral leishmaniasis caused by Leishmania donovani. PKDL treatment options are few and have severe limitations. In East-Africa, the standard treatment of PKDL is with daily painful potentially toxic sodium stibogluconate injections, administered for a prolonged duration of 30-60 days. In the Indian subcontinent, PKDL is mainly treated with miltefosine, a safer orally administered drug. However, in East-Africa, there is very limited experience in the use of miltefosine for treatment of severe PKDL, with only one published case report. Here we report a severe PKDL case in an Ethiopian HIV patient successfully treated with oral miltefosine (100mg/day for 28 days). Miltefosine was efficacious, safe and well tolerated, suggesting that it can play an important role in the treatment of severe PKDL also in East-African patients. Further research is warranted.

Assessment of hypertension management and control: a registry-based observational study in two municipalities in Cuba.

BACKGROUND: To determine the prevalence of hypertension treatment and control among hypertensive patients in the Cuban municipalities of Cardenas and Santiago and to explore the main associated predictors. METHODS: Cross-sectional study, with multistage cluster sampling, conducted between February 2012 and January 2013 in two Cuban municipalities. We interviewed and measured blood pressure in 1333 hypertensive patients aged 18 years or older. Hypertension control was defined as blood pressure lower than 140/90 mmHg. RESULTS: The mean age ± standard deviation (SD) of participants was 59.8 ± 14 years, the mean systolic and diastolic blood pressure ± SD was 130.0 ± 14.4 and 83.1 ± 9.0 mmHg respectively. The majority of patients (91, 95%CI 90-93) were on pharmacological treatment, 49% with a combination of 2 or more classes of drugs. Among diagnosed hypertensive patients 58% (95%CI 55-61) had controlled hypertension. There was no association between hypertension control and gender, age and socio-economic condition. Levels of hypertension control depended on health area and control furthermore was positively associated with post-primary education, not being obese and white ethnicity: adjusted Odds Ratio (95% CI) 1.71 (1.26-2.34), 1.43 (1.09-1.88) and 1.41 (1.09-1.81) respectively. CONCLUSIONS: The observed figures are outstanding at the international level and illustrate that hypertension treatment and control are achievable in a resource-constrained setting such as Cuba. The country's primary health care approach and social equity in access to health care can be seen as key determinants of this success. Nevertheless, there is still room for improvement, as over a third of patients did not have controlled hypertension.

Involving private practitioners in the Indian tuberculosis programme: a randomised trial.

OBJECTIVES: To assess a multicomponent intervention to improve private practitioners (PPs) involvement in referral of presumptive pulmonary TB (PTB) cases to the Revised National TB Control Programme (RNTCP) for sputum examination. METHODS: Randomised controlled trial. We randomly allocated all 189 eligible PPs in Tumkur city, South India, to intervention or control arm. The intervention, implemented between December 2014 and January 2016, included two sets of activities, one targeted at health system strengthening (building RNTCP staff capacity to collaborate with PPs, provision of feedback on referrals through SMS) and one targeted at intervention PPs (training in RNTCP, provision of referral pads and education materials and monthly visits to PPs by RNTCP staff). Crude and adjusted referral and PTB case-finding rate ratios were calculated with negative binomial regression. RESULTS: PPs referred 836 individuals (548 from intervention and 169 from control arm PPs) of whom 176 were diagnosed with bacteriologically confirmed PTB. The proportion (95% confidence interval) of referring PPs [0.59 (0.49, 0.68) vs. 0.42 (0.32, 0.52) in the intervention and control arm, respectively], mean referral rate per PP-year [(5.7 (3.8, 8.7) vs. 1.8 (1.2, 2.8)] and smear-positive PTB case-finding rate per PP-year [(1.5 (0.9, 2.2) vs. 0.6 (0.3, 0.9)] were significantly higher in the intervention than the control arm. Stratifying by qualification, a statistically significant difference in the above indicators remained only among GPs and internists. Overall, surgeons, paediatricians and gynaecologists referred few patients. PP referrals contributed to 20% of the sputum smear positive PTB cases detected by RNTCP in Tumkur city (14% were from intervention arm PPs). CONCLUSIONS: We demonstrated the effectiveness of a health system-oriented intervention to improve PP's referrals of presumptive PTB cases to RNTCP.

Patients pathways to tuberculosis diagnosis and treatment in a fragmented health system: a qualitative study from a south Indian district.

BACKGROUND: India's Revised National Tuberculosis (TB) Control Programme (RNTCP) offers free TB diagnosis and treatment. But more than 50% of TB patients seek care from private practitioners (PPs), where TB is managed sub-optimally. In India, there is dearth of studies capturing experiences of TB patients when they navigate through health facilities to seek care. Also, there is less information available on how PPs make decisions to refer TB cases to RNTCP. We conducted this study to understand the factors influencing TB patient's therapeutic itineraries to RNTCP and PP's cross referral practices linked to RNTCP. METHODS: We conducted in-depth interviews on a purposive sample of 33 TB patients and 38 PPs. Patients were categorised into three groups: those who reached RNTCP directly, those who were referred by PPs to RNTCP and patients who took DOT from PPs. We assessed patient's experiences in each category and documented their journey from initial symptoms until they reached RNTCP, where they were diagnosed and started on treatment. PPs were categorised into three groups based on their TB case referrals to RNTCP: actively-referring, minimally-referring and non-referring. RESULTS: Patients had limited awareness about TB. Patients switched from one provider to the other, since their symptoms were not relieved. A first group of patients, self-medicated by purchasing get rid drugs from private chemists over the counter, before seeking care. A second group sought care from government facilities and had simple itineraries. A third group who sought care from PPs, switched concurrently and/or iteratively from public and private providers in search for relief of symptoms causing important diagnostic delays. Eventually all patients reached RNTCP, diagnosed and started on treatment. PP's cross-referral practices were influenced by patient's paying capacity, familiarity with RNTCP, kickbacks from private labs and chemists, and even to get rid of TB patients. These trade-offs by PPs complicated patient's itineraries to RNTCP. CONCLUSIONS: India aims to achieve universal health care for TB. Our study findings help RNTCP to develop initiatives to promote early detection of TB, by involving PPs and private chemists and establish effective referral systems from private sectors to RNTCP.

Coping with tuberculosis and directly observed treatment: a qualitative study among patients from South India.

BACKGROUND: In India, the Revised National TB control programme (RNTCP) offers free diagnosis and treatment for tuberculosis (TB), based on the Directly Observed Treatment Short course (DOTS) strategy. We conducted a qualitative study to explore the experience and consequences of having TB on patients enrolled in DOTS and their caretakers in Tumkur district, located in a southern state of India, Karnataka. METHODS: We conducted 33 in-depth interviews on a purposive sample of TB patients from three groups: (1) patients who reached RNTCP directly on their own and took DOTS at RNTCP; (2) patients who were referred by private practitioners (PPs) to RNTCP and took DOTS at RNTCP; and (3) patients diagnosed by RNTCP and took DOTS from PPs. Data was analyzed using a thematic approach with the support of NVivo9. RESULTS: The study revealed that TB and DOTS have a large impact on patient's lives, which is often extended to the family and caretakers. The most vulnerable patients faced the most difficulty in accessing and completing DOTS. The family was the main source of support during patient's recovery. Patients residing in rural areas and, taking DOTS from the government facilities had to overcome many barriers to adhere to the DOTS therapy, such as long travelling distance to DOTS centers, inconvenient timings and unfavorable attitude of the RNTCP staff, when compared to patients who took DOTS from PPs. Advantages of taking DOTS from PPs cited by the patients were privacy, flexibility in timings, proximity and more immediate access to care. Patients and their family had to cope with stigmatization and fear and financial hardships that surfaced from TB and DOTS. Young patients living in urban areas were more worried about stigmatisation, than elderly patients living in rural areas. Patients who were referred by PPs experienced more financial problems compared to those who reached RNTCP services directly. CONCLUSION: Our study provided useful information about patient's needs and expectations while taking DOTS. The development of mechanisms within RNTCP towards patient centered care is needed to enable patients and caretakers cope with disease condition and adhere to DOTS.

A prospective longitudinal study of tuberculosis among household contacts of smear-positive tuberculosis cases in Lima, Peru.

BACKGROUND: Household contacts (HHCs) of TB cases are at increased risk for TB disease compared to the general population but the risk may be modified by individual or household factors. We conducted a study to determine incident TB among HHCs over two years after exposure and to identify individual and household level risk factors. METHODS: Adults newly diagnosed with a first episode of smear-positive pulmonary TB (index cases) between March 2010 and December 2011 in eastern Lima, were interviewed to identify their HHC and household characteristics. TB registers were reviewed for up to two years after the index case diagnosis and house visits were made to ascertain TB cases among HHC. The TB incidence rate ratio among HHCs as a function of risk factors was determined using generalized linear mixed models. RESULTS: The 1178 index cases reported 5466 HHCs. In 402/1178 (34.1 %) households, at least one HHC had experienced a TB episode ever. The TB incidence among HHCs was 1918 (95%CI 1669-2194) per 100,000 person-years overall, and was 2392 (95%CI 2005-2833) and 1435 (95%CI 1139-1787) per 100,000 person-years in the first and second year, respectively. Incident TB occurred more than six months following the index case's TB diagnosis in 121/205 (59.0 %) HHCs. In HHCs, bacillary load and time between symptoms and treatment initiation in the index case, as well as the relationship to the index case and the sex of the HHC all had a significant association with TB incidence in HHCs. CONCLUSIONS: Incidence of TB among HHCs was more than ten times higher than in the general population. Certain HHC and households were at higher risk of TB, we recommend studies to compare HHC investigation to households at highest risk versus current practice, in terms of efficiency.

Molecular epidemiology of tuberculosis in Havana, Cuba, 2009.

OBJECTIVES: To estimate the proportion of tuberculosis cases attributable to recent transmission and the risk factors possibly associated with tuberculosis clustering. METHODS: Population-based study combining information from epidemiological investigation of tuberculosis cases notified to the National Tuberculosis Control Program in Havana, Cuba, in 2009 with the results of genotyping of Mycobacterium tuberculosis isolates with variable number tandem repeat of mycobacterial interspersed repetitive units (MIRU-VNTR) typing. RESULTS: Of 186 cases, 61 were genotyped: 33 patterns and five clusters with 19, 7, 3, 2 and 2 cases were found. The proportion of cases due to recent transmission was 45% (95% confidence interval 33-58%). Routine contact investigation failed to identify a substantial number of epidemiological links. A history of living in a closed setting was strongly associated with clustering. CONCLUSIONS: The proportion of cases due to recent transmission in Havana in 2009 is high. The existing control measures in closed settings should be strengthened. A study on a larger number of cases and for a longer time period should be carried out to obtain more precise estimates. Further studies on the utility and cost-effectiveness of the addition of molecular epidemiology techniques to support the progress towards tuberculosis elimination in Cuba, a low-incidence resource-limited setting, are also needed.

Long-term evaluation of the risk of recurrence after cerebral sinus-venous thrombosis.

BACKGROUND: The clinical course of cerebral sinus-venous thrombosis (CSVT) is largely unknown because prospective studies with a long follow-up and with the goal to assess thrombosis recurrence rate and predisposing factors for recurrence are lacking. METHODS AND RESULTS: One hundred forty-five patients with a first CSVT were followed up for a median of 6 years after discontinuation of anticoagulant treatment. End points were recurrent CSVT or other clinical manifestations of venous thromboembolism. CSVT recurred in 5 patients (3%) and other manifestations of venous thromboembolism (deep vein thrombosis of the lower limbs or pulmonary embolism) were seen in 10 additional patients (7%), for a recurrence rate of 2.03 per 100 person-years (95% confidence interval, 1.16 to 3.14) for all manifestations of venous thromboembolism and 0.53 per 100 person-years (95% confidence interval, 0.16 to 1.10) for CSVT. Nearly half of the recurrences occurred within the first year after discontinuation of anticoagulant therapy. Risk factors for recurrent venous thrombosis were male sex (adjusted hazard ratio, 9.66; 95% confidence interval, 2.86 to 32.7) and, for thromboses other than CSVT, severe thrombophilia resulting from antithrombin, protein C, protein S deficiency, anti-phospholipid antibodies, or combined abnormalities (adjusted hazard ratio, 4.71; 95% confidence interval, 1.34 to 16.5). CONCLUSIONS: The risk of recurrent CSVT is low and is higher in the first year after discontinuation of anticoagulant treatment and among men. Mild thrombophilia abnormalities are not associated with recurrent CSVT, but severe thrombophilia entails an increased risk of deep vein thrombosis of the lower limbs or pulmonary embolism.

High levels of factor VIII and risk of extra-hepatic portal vein obstruction.

BACKGROUND/AIMS: High levels of coagulation factor VIII are a risk factor for lower-limb deep vein thrombosis (DVT). Their role in extra-hepatic portal vein obstruction (EHPVO) is not established. METHODS: Factor VIII was measured in 85 patients with EHPVO (primary in 58 and complicating liver cirrhosis in 27), in 200 with lower-limb DVT, in 108 with liver cirrhosis without thrombosis and in 200 healthy controls. RESULTS: Factor VIII levels were significantly higher in patients with primary EHPVO (138 IU/dL, range 86-366), EHPVO and cirrhosis (147 IU/dL, 95-242), lower-limb DVT (140 IU/dL, 64-400) and cirrhosis alone (160 IU/dL, 43-446) than in controls (112 IU/dL, 62-250, p<0.001). When factor VIII exceeded 129 IU/dL (66th percentile), the odds ratios were 10.5 (95%CI 3.3-33.4) for primary EHPVO, 6.0 (1.2-30.7) for EHPVO and cirrhosis, 5.0 (2.6-9.4) for lower-limb DVT. After exclusion of the effect of the acute phase reaction, the odds ratio for primary EHPVO was 4.2 (0.8-22.7), and was 8.7 (0.9-80.5) after exclusion also of patients with chronic myeloproliferative disorders. CONCLUSIONS: High factor VIII levels are independently associated with an increased risk for EHPVO. The risk of EHPVO increased with increasing factor VIII levels and was only partially dependent on the acute phase reaction.

ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission.

BACKGROUND: From 20 to 50% of patients who survive an acute episode of the acquired form of thrombotic thrombocytopenic purpura relapse but clinical and laboratory markers of recurrence are not well established. DESIGN AND METHODS: In 109 patients enrolled in an international registry we evaluated, in the frame of a retrospective cohort study, the predictive role of the metalloprotease ADAMTS13 as measured in plasma during remission. Anti-ADAMTS13 antibodies and von Willebrand factor were also evaluated in a smaller number of the same patients. RESULTS: Median values of ADAMTS13 activity and antigen were significantly lower in patients with recurrent thrombotic thrombocytopenic purpura than in those with no recurrence (activity: 12% vs. 41%; p=0.007; antigen: 36% vs. 58%; p=0.003). A severe deficiency of ADAMTS13 activity (10% or less) was associated with a higher likelihood of recurrence (odds ratio 2.9; 95% confidence interval 1.3 to 6.8; p=0.01). Anti-ADAMTS13 antibodies were also more prevalent in patients with recurrent thrombotic thrombocytopenic purpura (odds ratio 3.1; 95% confidence interval 1.4 to 7.3; p=0.006). The presence during remission of both severe ADAMTS13 deficiency and anti-ADAMTS13 antibodies increased the likelihood of recurrence 3.6 times (95% confidence interval 1.4 to 9.0; p=0.006). The presence of ultralarge von Willebrand factor multimers and of associated diseases or conditions did not increase recurrence. CONCLUSIONS: Survivors of an acute episode of acquired thrombotic thrombocytopenic purpura with severely reduced levels of ADAMTS13 and/or with anti-ADAMTS13 antibodies during remission have an approximately three-fold greater likelihood of developing another episode of thrombotic thrombocytopenic purpura than patients with higher protease activity and no antibody.

Hormone therapy and thromboembolic disease.

PURPOSE OF REVIEW: Hormone therapy increases the risk of venous thromboembolism (VTE). To reduce this risk, changes in dosage, composition and route of administration have been made over the years. This review provides a summary of the available evidence and an update on the most recent findings on the issue. RECENT FINDINGS: Contraceptives containing third-generation progestagens confer a higher risk of VTE than second-generation compounds. Little data are available on preparations containing less than 30 micarog of estrogen, new progestagens or levonorgestrel-releasing intrauterine devices. Hormone replacement therapy increases the risk of VTE by 2 to 3-fold. Transdermal administration may be less thrombogenic than oral administration, while different estrogens and progestagens may carry a different risk. VTE risk is further increased in carriers of inherited thrombophilia. Despite a similar increase in relative risk of thrombosis associated with hormone therapy, absolute risk is lower in fertile women and higher in postmenopausal ones. Universal screening for thrombophilia before prescribing hormone replacement therapy might be cost-effective. SUMMARY: Careful evaluation of individual risk factor is warranted before prescribing hormone therapy. Further investigations are needed to establish whether or not newer compounds are safer than older ones with respect to the risk of thrombosis.

The endogenous thrombin potential and the risk of venous thromboembolism.

BACKGROUND: The risk of venous thromboembolism (VTE) is increased by an excess of procoagulant or by a defect of anticoagulant proteins, with circumstantial risk factors playing a significant contribution. These conditions are directly linked to or are compatible with increased thrombin generation. Assuming that the more thrombin is generated the higher is the risk of VTE, an overall coagulation test monitoring ex vivo thrombin generation and reflecting the interaction of pro- and anticoagulant proteins would be useful to determine the risk of VTE. PATIENTS AND METHODS: This hypothesis was tested by measuring the endogenous thrombin potential (ETP) without or with thrombomodulin (TM) in plasmas from 403 individuals stratified according to their relative risk of VTE (no, low, intermediate, or high risk) according to whether or not they had congenital and/or circumstantial risk factors. Odds ratio (OR) and 95% confidence interval (CI), taken as a measure of the relative risk of having high levels of ETP, were calculated for the different categories relatively to the no-risk category. RESULTS: When the ETP was measured with TM, ORs (95% CI) were 2.10 (1.23-3.60); 4.03 (2.18-7.45) and 4.96 (2.40-10.23) for the low-, intermediate and high-risk category. When ETP was measured without TM there was no gradient of OR values as function of the risk category. CONCLUSIONS: ETP measured with TM may help to distinguish individuals with different risk of VTE, however, the practical utility of measuring ETP in clinical practice remains to be evaluated in prospective studies.

The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis.

Whether or not pregnant women with a previous episode of venous thromboembolism (VTE) should receive antithrombotic prophylaxis is a matter of debate. In order to estimate the rate of recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE) during pregnancy and puerperium we retrospectively investigated a cohort of 1104 women with previous VTE; after a single DVT or isolated PE, 88 of them became pregnant at least once without receiving antithrombotic prophylaxis. Overall, 155 pregnancies and 120 puerperium periods without prophylaxis were recorded. There were nine recurrences during pregnancy and 10 during puerperium, with a rate of 5.8% [95% confidence interval (CI) 3.0-10.6] and 8.3% (95%CI 4.5-14.6) respectively. In pregnancy, the rate of recurrence was 7.5% (95%CI 4.0-13.7) if the first VTE was unprovoked, related to pregnancy or to oral contraceptive use, whereas no recurrence occurred if the first VTE was related to other transient risk factors. In puerperium, the rate of recurrence was 15.5% (95%CI 7.7-28.7) in women with a pregnancy-related first VTE, with a risk 3.9-times higher than in the remaining women. Inherited thrombophilia was not associated with a statistically significant increase in risk of recurrence in pregnancy or in puerperium, yet the rate of recurrence in puerperium was 14.2% (95%CI 5.7-31.4) in overall carriers of factor V Leiden and 30% (95%CI 10.7-60.3) in carriers with a pregnancy-related first VTE, with a risk 6.8 times higher than in women without thrombophilia and with a non pregnancy-related first VTE.

Oral contraceptive use, thrombophilia and their interaction in young women with ischemic stroke.

To investigate the role of oral contraceptives and their interaction with thrombophilia in ischemic stroke, a case-control study on women with a first ischemic stroke when younger than 45 years was carried out. Oral contraceptives doubled the risk of ischemic stroke in the first 6-18 months of use and hyperhomocysteinemia increased the risk by 3.5-fold. Carriers of factor V Leiden or prothrombin G20210A were not found to have a statistically significant increased risk. The risk of ischemic stroke in oral contraceptive users was 13 times higher in women who were also carriers of factor V Leiden and 9 times higher in those who also had hyperhomocysteinemia.