Mortality Related to Chronic Obstructive Pulmonary Disease and Co-morbidities in the United States,A Multiple Causes of Death Analysis

ABSTRACT

Chronic obstructive pulmonary disease (COPD) mortality based on the underlying cause of death (UCOD) underestimates disease burden. We aimed to determine the current COPD mortality rate, trends and the distribution of co-morbidities using United States (US) multiple-cause of death (MCOD) records.

All 38,905,575 death certificates of decedents aged ≥45 years in the United States were analyzed for 1999–2015. COPD was defined by ICD–10 codes J40–J44 and J47 based either on the UCOD or up to 20 contributing causes coded. Annual age–standardized COPD death rates were computed by age, gender and race/ethnicity for those with any mention of COPD.

In 2015, COPD was mentioned in 11.59% (292,572 deaths) in MCOD, compared to 11.13% (243,617 deaths) in 1999, a 4% increase. However, it was reported as the UCOD for only 5.56% and 4.97% in 2015 and 1999 respectively, an 11% increase. The most common UCOD in subjects with any mention of COPD was respiratory disorders in 49% of males and 55% of females. The relative change in death rates differed between MCOD and UCOD. For example, among non-Hispanic white females aged 65–74 years the UCOD rate per 100,000 (95% CI) decreased from 163 (160–166) to 147 (145–150), average annual percent decrease (AAPD) –0.26, while the MCOD rate decreased from 308 (304–311) to 263 (260–267), AAPD –0.87.

Statistics based on UCOD understated the burden of COPD in the United States. MCOD rates were twice as high as UCOD rates. The relative change in death percent or rates differed between MCOD and UCOD. MCOD analysis should be repeated periodically to help evaluate the burden of COPD-related mortality.     

Monocytes and neutrophils from tuberculosis patients are insensitive to anti-inflammatory effects triggered by the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP)

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis where formyl peptides, which are cleavage products of bacterial and mitochondrial proteins, are present. In this study, we demonstrated that interferon gamma (IFN)-gamma and interleukin (IL)-10 induced the overexpression of the receptor for the Fc portion of IgG I (FcgammaRI) in monocytes from tuberculosis (TB) patients, showing that these cells respond to IFN-gamma and IL-10 signals. We also demonstrated that lower doses of IL-10 render monocytes from TB patients less responsive to higher doses of the cytokine. Although the prototypic formyl peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) is a well-known proinflammatory agonist, we have demonstrated previously that preincubation of monocytes with FMLP inhibited the up-regulation of FcgammaRI induced by IFN-gamma or IL-10. This effect was not observed in monocytes from TB patients. FMLP also induced the down-regulation of the expression of FcgammaRI in monocytes that had been activated already with IFN-gamma. However, this effect of FMLP was not observed in monocytes from TB patients and supernatants from monocytes obtained from these patients were incapable of inducing the down-regulation of FcgammaRI. In contrast to normal donors, supernatants from FMLP-treated neutrophils from TB patients did not modify the basal level of expression of FcgammaRI in monocytes from normal donors. In conclusion, in this study we demonstrated the existence of two novel mechanisms that may contribute to the pathological effects generated by M. tuberculosis: the enhancement of FcgammaRI in response to IFN-gamma and IL-10, and the unresponsiveness to the anti-inflammatory effects induced by formyl peptides.     

Patients' characteristics and clinical implications of suboptimal CD4 T-cell gains after 1 year of successful antiretroviral therapy

To describe characteristics and prognosis of patients with suboptimal immunological response to combined antiretroviral therapy (CART). Using data from a multicenter cohort study, we selected patients who initiated CART and showed suboptimal CD4-T cell response (defined as <50 cells/L increase) after 1 year of therapy, despite sustained virological suppression. Characteristics of those patients were compared with subjects who showed optimal immunological response. Of 650 patients with virological suppression, 108 (16.6%) showed suboptimal CD4-T cell response. Independent predictors of suboptimal response were previous injection drug use (OR, 1.85; 95% CI, 1.12-2.98) and age at CART initiation (OR, 1.04 per year increase; 95%CI, 1.01-1.06). Hepatitis C virus coinfection was not associated with impaired immunological response. As compared with patients with optimal immunological response, those with suboptimal response had a higher mortality rate (3.22 versus 0.71 per 100 person-years; p=.001), but a similar rate of new AIDS-defining events. In patients with sustained virological suppression with CART, previous injection drug use, but not hepatitis C virus coinfection, and older age at initiation of therapy were associated with suboptimal CD4 T-cell responses. Patients with suboptimal response had a higher mortality over time, mainly due to diseases other than AIDS-defining events.     

Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine comprising a synthetic antigen in healthy adults

The combined HB-Hib vaccine candidate Hebervac HB-Hib (CIGB, La Habana), comprising recombinant HBsAg and tetanus toxoid conjugate synthetic PRP antigens has shown to be highly immunogenic in animal models. A phase I open, controlled, randomized clinical trial was carried out to assess the safety and immunogenicity profile of this bivalent vaccine in 25 healthy adults who were positive for antibody to HBsAg (anti-HBs). The trial was performed according to Good Clinical Practices and Guidelines. Volunteers were randomly allocated to receive the combined vaccine or simultaneous administration of HB vaccine Heberbiovac-HB and Hib vaccine QuimiHib (CIGB, La Habana). All individuals were intramuscularly immunized with a unique dose of 10 microg HBsAg plus 10 microg conjugated synthetic PRP. Adverse events were actively recorded after vaccine administration. Total anti-HBs and IgG anti-PRP antibody titers were evaluated using commercial ELISA kits at baseline and 30 days post-vaccination. The combined vaccine candidate was safe and well tolerated. The most common adverse reactions were local pain, febricula, fever and local erythema. These reactions were all mild in intensity and resolved without medical treatment. Adverse events were mostly reported during the first 6-72 hours post-vaccination. There were no serious adverse events during the study. No severe or unexpected events were either recorded during the trial. The combined vaccine elicited an anti-HBs and anti-PRP booster response in 100% of subjects at day 30 of the immunization schedule. Anti-HBs and anti-PRP antibody levels had at least a two-fold increase compared to baseline sera. Even more, anti-HBs antibody titer showed a four-fold increase in 100% of volunteers in the study group. The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens. To our knowledge, this is the first demonstration of safety and immunogenicity for a combined vaccine comprising recombinant HBV and synthetic Hib antigens. The present results support phase I-II clinical trial in the target population, two months old healthy infants.     

Cirugía de rescate en el cáncer colorrectal metastásico

El objetivo del estudio es el análisis de la supervivencia en el cáncer colorrectal metastásico tras la cirugía de rescate. Entre 1991 y 1998 se diagnosticaron 498 pacientes con cáncer colorrectal. En 10 pacientes se realizó cirugía de rescate de metástasis metacrónicas hepáticas o pulmonares. Se analizaron las características clínicas, el tratamiento realizado y la supervivencia. Siete fueron hombres y 3 mujeres con edades comprendidas entre 36–75 años (mediana: 61 años). La localización más frecuente fue recto seguida de sigma. Sólo 3 pacientes tenían afectación ganglionar. La localización más frecuente de las metástasis fue hepática, seguida de pulmonar. El nÚmero de metástasis fue 3 en un paciente, 2 en 3 pacientes y en el resto fue Única. El tamaño osciló entre 2 y 6,5 cm. La mediana del intervalo libre de enfermedad hasta el diagnóstico de la metástasis fue de 17 meses (rango: 8–48). El intervalo libre de enfermedad tras metastasectomía fue de 15,5 meses de mediana (rango: 3–72). La mediana del tiempo de seguimiento fue 47 meses (rango: 19–97). La cirugía de rescate de las metástasis hepáticas y pulmonares del cáncer colorrectal puede ofrecerun aumento de la supervivencia en pacientes seleccionados.