Cost-effectiveness of elbasvir/grazoprevir use in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and chronic kidney disease in the United States.

Among patients with chronic kidney disease (CKD) in the United States, HCV infection causes significant morbidity and mortality and results in substantial healthcare costs. A once-daily oral regimen of elbasvir/grazoprevir (EBR/GZR) for 12 weeks was found to be a safe and efficacious treatment for HCV in patients with CKD. We evaluated the cost-effectiveness of EBR/GZR in treatment-naïve and treatment-experienced CKD patients compared with no treatment (NoTx) and pegylated interferon plus ribavirin (peg-IFN/RBV) using a computer-based model of the natural history of chronic HCV genotype 1 infection, CKD and liver disease. Data on baseline characteristics of the simulated patients were obtained from NHANES, 2000-2010. Model inputs were estimated from published studies. Cost of treatment with EBR/GZR and peg-INF/RBV were based on wholesale acquisition cost. All costs were from a third-party payer perspective and were expressed in 2015 U.S. dollars. We estimated lifetime incidence of liver-related complications, liver transplantation, kidney transplantation, end-stage live disease mortality and end-stage renal disease mortality; lifetime quality-adjusted life years (QALY); and incremental cost-utility ratios (ICUR). The model predicted that EBR/GZR will significantly reduce the incidence of liver-related complications and prolong life in patients with chronic HCV genotype 1 infection and CKD compared with NoTx or use of peg-IFN/RBV. EBR/GZR-based regimens resulted in higher average remaining QALYs and higher costs (11.5716, $191 242) compared with NoTx (8.9199, $156 236) or peg-INF/RBV (10.2857, $186 701). Peg-IFN/RBV is not cost-effective, and the ICUR of EBR/GZR compared with NoTx was $13 200/QALY. Treatment of a patient on haemodialysis with EBR/GZR resulted in a higher ICUR ($217 000/QALY). Assuming a threshold of $100 000 per QALY gained for cost-effectiveness, use of elbasvir/grazoprevir to treat an average patient with CKD can be considered cost-effective in the United States.

Location of the vector of jaw muscle force in mammals.

Previous work has suggested that the third molar lies just in front of the point where the resultant vector of jaw muscle force, estimated from dissections, intersects the tooth row. This point meets the jaw such that the vector is 30% of jaw length from the jaw joint. Thus, the vector divides the jaw in the ratio of 3:7 when measurements are taken perpendicular to the vector. In practice, however, distances along mammalian jaws are typically measured on an easily determined line such as a line from one end of the tooth row to the other. The position of the jaw joint is then projected onto this line. As a rule, such a line is not perpendicular to the vector and so the distance from the projection of the joint, out to the rear of the third molar (and the vector's intersection), is different in different mammals. Rarely is this distance 30% of total jaw length. However, when the location of the vector's intersection is measured along the tooth row, this position varies directly with the inclination of the vector; a vector inclined posteriorly intersects the tooth row far from the projection of the joint and an anterior vector's intersection is relatively close. Only a vector perpendicular to the line from one end of the tooth row to the other intersects at 30%. This obvious point suggests a way to test the above hypotheses when the inclination of the vector is not known exactly. The predicted relationship between the distance to the molar, as a percentage of the total jaw length, and the approximate inclination of the vector derived from muscle weights (posterior or anterior depending on whether the temporalis or the masseter/pterygoid, respectively, is dominant) was observed in a sample of 46 different mammals.

A multicenter, randomized, double-blind, placebo-controlled trial of recombinant human interleukin-10 in HIV-infected subjects.

OBJECTIVE: To determine the effect of multiple subcutaneous doses of recombinant human interleukin (rhuIL)-10 on plasma HIV RNA levels and CD4 T-cell counts, and to evaluate its safety and tolerability in HIV-infected subjects. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. SUBJECTS: Thirty-nine HIV-infected subjects with CD4 T-cell counts > 200 x 10(6)/l, plasma HIV RNA concentrations > or = 3.18 log10 copies/ml and on stable antiretroviral therapy were recruited from six centers. INTERVENTION: Subjects received (subcutaneously) rhuIL-10 1 microg/kg daily, 4 microg/kg daily, 8 microg/kg three times per week, placebo daily or placebo three times per week for 4 weeks. MAIN OUTCOME MEASURES: Prospectively defined outcomes included safety and tolerability, plasma HIV RNA levels and CD4 T-cell counts. Outcomes were assessed at baseline, weeks 1, 2, 3 and 4 during treatment and weeks 2 and 4 following completion of therapy. RESULTS: Baseline characteristics were similar in all groups. Compared to baseline, no significant change in plasma HIV RNA concentrations or CD4 T-cell counts was observed in any of the groups. RhuIL-10 was generally well tolerated. Two patients receiving rhuIL-10 4 microg/kg required discontinuation due to thrombocytopenia. One patient receiving rhuIL-10 4 microg/kg who had chronic hepatitis B and C infections discontinued drug because of elevated liver function tests. One patient receiving placebo discontinued study drug because of depression. CONCLUSION: The lack of a demonstrable virological benefit, as assessed by plasma viral load, with 4 weeks of rhuIL-10 does not support the development of this immune-based therapy for treatment of HIV infection.

A multicenter, randomized, controlled trial of three preparations of low-dose oral alpha-interferon in HIV-infected patients with CD4+ counts between 50 and 350 cells/mm(3). Division of AIDS Treatment Research Initiative (DATRI) 022 Study Group.

To evaluate the effectiveness of low-dose oral alpha-interferon (alpha-IFN), 247 HIV-infected study subjects received placebo, Alferon LDO, Veldona, or Ferimmune in a randomized, double-blind trial. Subjects had CD4+ counts between 50 and 350 cells/mm3 and HIV-related symptoms at entry. Study subjects rated the severity of eight symptoms using a symptom burden index (SBI). Study endpoints included changes in SBI, weight, CD4+ count, and Karnofsky score between baseline and the 24-week visit. The SBI outcome and weight were measured in 99 and 106 study subjects, respectively, at both the baseline and 24-week visits. Baseline SBI scores ranged from 5.4 to 7.9 in the four arms. No clinically important or statistically significant differences were found among the four arms with regard to SBI or weight change over the 24-week period. There were also no significant differences among the arms for CD4+ cell count and Karnofsky score. Few adverse reactions were noted in any arm, and there were no significant differences between arms. Although the trial was designed to enroll 560 study subjects and was prematurely terminated because of slow accrual and discontinuations of participants, the small differences among the arms in the primary and secondary endpoints do not support claims of efficacy for the measures studied.

Pneumococcal bacteremia in adults: a 14-year experience in an inner-city university hospital.

We retrospectively reviewed 304 episodes of pneumococcal bacteremia in 293 adults to compare the clinical features, prognostic factors, and case-fatality rate associated with this illness to those in previous studies. We studied patients at an inner-city university hospital who had pneumococcal bacteremia from January 1980 through December 1993. We analyzed patient demographics, risk factors for pneumococcal infection, pneumococcal vaccination status, initial vital signs, findings on chest roentgenograms, arterial blood gases, and laboratory values. Ninety-six percent of our study population was African American and 61% were male; pneumococcal vaccination was documented for 2%. The case-fatality rate in our study was 36%. Older age, lower mean arterial pressure, lower mean temperature, higher respiratory rate, multilobar pneumonia, leukopenia, low platelet count, hypoalbuminemia, low arterial pH, low arterial oxygen tension, and high arterial carbon dioxide tension were associated with higher mortality. Our study suggests that mortality due to pneumococcal bacteremia has not changed significantly in the last 6 decades, that the number of patients in high-risk groups who are receiving pneumococcal vaccine is insufficient, and that higher mortality can be predicted from the history, vital signs, and laboratory values at initial presentation.

Renal infection due to adenovirus in a patient with human immunodeficiency virus infection.

Opportunistic viral infections in persons with human immunodeficiency virus (HIV) infection are well described, but reports of morbidity or mortality caused by adenoviruses among this patient population are uncommon despite the frequent isolation of adenoviruses from patients with HIV infection. At autopsy we found necrotizing adenovirus infection of renal tubules in a patient with cytomegalovirus infection of the colon and adrenal glands. The tissue damage we describe in this report adds to the spectrum of findings for patients with asymptomatic adenovirus infection of the urinary tract.

The amateur Radio Emergency Service (ARES) and the National Disaster Medical System (NDMS).

The rescue, treatment, and evacuation of thousands of patients from a natural disaster or armed conflict that is coordinated by the National Disaster Medical System must be performed in accordance to health care standards recognized in this country. Without an effective communication system, morbidity and mortality will needlessly rise. A medical communication protocol that addresses this problem is proposed.

Autopsy findings in HIV-infected inner-city patients.

To assess the importance of the autopsy in HIV-1 infection, we retrospectively reviewed the autopsy reports of 70 HIV-1-seropositive patients at Howard University Hospital. Of the 58 patients with AIDS, the diagnosis of AIDS was made after autopsy in 24 (41%) cases. The lung was the most common site of AIDS-diagnostic diseases, and was affected in 90% of patients. Pneumocystis carinii infection was the most common AIDS-diagnostic disease, and was present in 50% of the AIDS patients. Thirty-eight percent of AIDS diagnostic diseases were diagnosed antemortem, including 15 of the 29 Pneumocystis carinii infections. Most of the AIDS-diagnostic diseases were disseminated at autopsy and two or more diseases were found in some organs. Overall, Pneumocystis carinii pneumonia was the most common cause of death, accounting for a mortality of 43% among AIDS patients. Bacterial infections were common and contributed to the mortality and morbidity of both AIDS and non-AIDS patients. Bacterial infection was the cause of death in 15 AIDS and 9 non-AIDS patients. The clinical cause of death concurred with the pathological cause in 53% of our cases.

Pneumococcal sepsis and meningitis in adults with sickle cell disease.

Patients with sickle cell disease are predisposed to infection caused by Streptococcus pneumoniae. However, there has been only one published case of bacteremic pneumococcal meningitis in an adult with sickle cell anemia. We report here the cases of six adults with sickle cell disease, pneumococcal sepsis, and meningitis. Five patients were male and one was female. Their ages ranged from 18 to 34 years (mean, 25.7 years). Five patients had the SS and one had the SC hemoglobin phenotype. Only one patient had received pneumococcal vaccine (14 valent). This vaccine did not protect against the pneumococcal serotype causing his infection. All patients had high fever (mean, 39.8 degrees C [103.7 degrees F]) on admission; five had generalized weakness and four had neck stiffness. Leukocyte counts were greater than 30,000/mm3 in all patients. Streptococcus pneumoniae was isolated from the blood and the cerebrospinal fluid in all patients. The cerebrospinal fluid showed pleocytosis in six patients, an elevated protein level in five, and hypoglycorrhachia in two. Complications included renal failure in four patients, disseminated intravascular coagulation in one, and seizures in another. Two patients died. Pneumococcal sepsis and meningitis are uncommon in adults with sickle cell disease, but they carry a high morbidity and mortality. Wider use of the new 23-valent polysaccharide vaccine in these patients is recommended.

Metabolics and biologicals in the workplace.

Potential decrements in job performance are associated with a wide variety of pharmaceutical agents, including antimetabolites, antineoplastics, gout medications, biologicals, hormones, plasma fractions, and antibiotics. The number of potential employees taking these medications ranges from less than 1 in 1000 for the antineoplastics in 1 in 10 for some biologicals. Whether a particular employee will experience a medication-induced performance decrement with these medications, as well as the extent of such a decrement, is in large part a function of factors such as individuality in drug response, the employee's age and diet, and drug interactions.

Physician reaction to a local community cholesterol screening program.

One of the primary concerns of the National Cholesterol Education Program about mass screening for elevated blood cholesterol has been the readiness of primary care physicians to deal with a large number of referrals. After 11,680 people were screened in a city of 85,000 people, 3069 (26.3%) were referred to their private physicians. Three months later a questionnaire was mailed to 76 local primary care physicians, and a follow-up letter was mailed to those who had not responded after 2 months. The response rate was 76% from a total of seven specialties, primarily internal medicine and family medicine. Seventy-nine percent of the physicians had been aware of the program, 40% diagnosed at least one case of hypercholesterolemia as a result of the program, and 71% approved of community cholesterol screening. Only one physician indicated that he was overwhelmed with referrals. We conclude that most primary-care physicians support community cholesterol screening as a public health measure and will use screening data to initiate diagnosis.

Congenital rubella syndrome in the United States, 1970-1985. On the verge of elimination.

The National Congenital Rubella Syndrome Registry, a passive surveillance system, and the Birth Defects Monitoring Program, a newborn hospital discharge data set, are used to monitor the incidence of congenital rubella syndrome in the United States. Reports to the registry contain clinical and laboratory data which allow cases to be classified into six categories according to the likelihood of having congenital rubella syndrome. The monitoring program records newborn discharge diagnoses, without detailed information, of a nonrandom sample of about one fourth of the births in the United States annually. To evaluate the two systems and to estimate the actual incidence of congenital rubella syndrome, the authors collected hospital discharge summaries on all cases as reported by the monitoring program from 1970-1985 and classified them by the registry criteria. Of the 392 cases reported to the monitoring program during 1970-1985, 24% (n = 93) could be classified as confirmed or compatible compared with 79% (n = 415) of the 526 cases reported to the registry (rate ratio = 3.3; 95% confidence interval (CI) 2.9-3.8). Diagnosis of congenital rubella syndrome was made during the neonatal period for 68% (263 of 389) registry cases for whom such data were available. When the Lincoln-Peterson capture-recapture method of estimating population size for independent surveillance systems was used, an estimated 1,064 confirmed and compatible cases (95% CI 668-1,460) diagnosed during the neonatal period occurred during 1970-1979, for an average of 106 cases per year. During 1980-1985, an estimate of 122 neonatal confirmed and compatible cases (95% CI 8-236) occurred, for an average of 20 cases per year. A downward secular trend in the incidence of congenital rubella syndrome beginning in 1980 was observed. The registry detected 22% of all neonatal confirmed and compatible cases, the monitoring program detected 8%, and the two systems combined detected a total of 28%. The results indicate that congenital rubella syndrome may be on the verge of elimination in the United States.

Clindamycin versus metronidazole in the treatment of bacterial vaginosis.

One hundred forty-three women with complaints of vaginitis were assigned to receive either 500 mg of metronidazole twice daily for 7 days or clindamycin 300 mg twice daily for 7 days. There was no significant difference in the failure rate between patients treated with clindamycin (6.1%) and those treated with metronidazole (4%). Adverse reactions were infrequent and mild in both treatment groups. Three patients who received clindamycin developed non-bloody diarrhea, which was mild and did not necessitate discontinuing therapy. We conclude that clindamycin may be a safe and effective alternative to metronidazole for treating women with bacterial vaginosis.

A functional consequence of an ossified mandibular symphysis.

According to most recent workers, the presence of fused symphyses in some mammals is explained by the common view that muscle force is transmitted better across a fused, as opposed to an unfused, mandibular symphysis. Recent theoretical work has cast doubt on the importance of fusion for simple force transmission by suggesting that force can also be transmitted efficiently across an unfused symphysis, an expectation that has since been confirmed by a number of observational studies. Perhaps the real significance of symphyseal fusion is that, in animals with upper and lower incisor tooth rows that apply large forces to relatively small resistant food items, muscle force from both sides of the head is reliably available only when the symphysis is fused. Independent movement between the two sides of the lower incisor row, permitted by a patent symphysis, allows the possibility that one side of the lower row will come into contact with the upper incisor row, dissipating all of the muscle force from that side. The dissipation of approximately half of the available jaw muscle force, allowed by a patent symphysis, cannot be ignored when attempting to explain the presence of fused symphyses if one accepts the idea that strong incisor biting is an important element in the masticatory apparatus of those primates and other mammals with fused mandibular symphyses.