George Panos

A meta-analysis of transient elastography for the detection of hepatic fibrosis.

Objectives The use of transient elastography to assess liver stiffness measurement (LSM) has now become widely available for the diagnosis of liver fibrosis as a rapid, noninvasive test (it is still not approved for use in the United States). It has previously been showed as an accurate method of representing the state of liver fibrosis with concomitant evaluation of liver biopsy and the histologic scoring system METAVIR. We performed a meta-analysis to further assess its use in comparison with liver biopsy. Methods Studies from the literature were analyzed with a median liver stiffness value in kilopascal given for fibrosis stages according to histopathologic findings on biopsy and best discriminant cutoff levels in kilopascals for significant fibrosis (≥F2) and cirrhosis (F4). Results A total of 22 studies were selected comprising 4430 patients; chronic hepatitis C infection was the most common etiology of fibrosis. The pooled estimates for significant fibrosis (≥F2) measured 7.71u2009kPa (LSM cutoff value) with a sensitivity of 71.9% [95% confidence interval (CI): 71.4%-72.4%] and specificity of 82.4% (95% CI: 81.9-82.9%), whereas for cirrhosis (F4) the results showed a cutoff of 15.08u2009kPa with a sensitivity of 84.45% (95% CI: 84.2-84.7%) and specificity of 94.69% (95% CI: 94.3%-95%). Conclusions Further evaluation of transient elastography to assess LSM is required in prospective studies to potentially increase the sensitivity and establish its clinical utility.

Worldwide Prevalence of Head Lice

To the Editor: Pediculosis capitis has been well-known since antiquity (1). Human infestation can result in psychological frustration for parents and children (2); furthermore, preventive and therapeutic practices, such as head shaving and the “no-nit” policy of excluding infected children from school, can also induce social stress. n nWe sought to synthesize the available evidence regarding the worldwide prevalence of lice infestation in the 21st century by conducting a literature search of PubMed and Scopus databases in which we searched for the term pediculosis. We also searched Google for the terms head lice/pediculosis capitis and individual country names and evaluated references of the articles and reports retrieved through this search. Eligible studies were archived from January 1, 2000, to January 18, 2008. n nWe retrieved 55 studies (Technical Appendix). Most studies referred to schoolchildren, but some involved refugees, urban slums, child labor, jails, orphanages, and fishing communities. n nMost studies had been conducted in Asia; Turkey was overrepresented. Prevalence varied from 0.7% to 59% and was higher in girls and women. Of the 29 studies, 24 involved schoolchildren; the other studies involved refugee children, child laborers, the general population, street children, jail inmates, and children accompanying their mothers in prison. n nIn Europe, prevalence varied from 0.48% to 22.4%. However, 1 study reported a much higher annual incidence (37.4%) in England (3). A study in the Ukraine showed increasing adult representation in the overall affected population (4). Six studies involved schoolchildren; the remaining studies involved refugees, homeless persons, and the general population. n nData from Africa, with the exception of 1 study in South Africa, were derived from Egypt. Prevalence varied from 0% to 58.9% and was higher in females. The study in South Africa (5) challenges the generally accepted concept that head lice infestation refers to lower socioeconomic status; of 2 schools, 1 in a low socioeconomic status area, populated by black students only, and the other in a high socioeconomic status area, populated by students of various races, head lice infestation was found only in the second school, solely among white pupils. Of 6 studies in Egypt, 4 involved diverse populations: urban poor preschool children, orphanage children, and the general population. n nMost studies in the Americas were conducted in Brazil, although we also found data from the United States, Cuba, and Argentina. Prevalence varied from 3.6% to 61.4% and was higher in females. Of 7 studies, 4 involved populations other than schoolchildren to some extent: urban slum residents, fishing community residents, adolescents and adults sampled randomly from the general population, elderly nursing home residents, and persons living with repeatedly infested children. A recent study in Brazil (6) noted that prevalence rates determined by visual inspection are twice that of rates determined by hair analysis. n nOnly 1 study has been performed in Oceania. This study in Australia reported prevalence of 13% and that girls were more likely to have active infection. n nOur review shows that pediculosis capitis is widespread throughout the world and does not discriminate on socioeconomic status grounds. The traditional perception of head lice as a parasitosis exclusively associated with schoolchildren of low socioeconomic status is challenged by some of the reports (Technical Appendix). n nMost studies underestimate overall prevalence by assessing it in a specific timeframe; to the contrary, head lice infestation is a dynamic process that can spread hypergeometrically in closed environments such as schools and in the community (7). The point-prevalence reported by Heukelbach et al (8) may represent a more accurate indicator. n nAlthough socioeconomic status seems to be an indicator of the magnitude of lice infestation, more specific determinants are the dynamic processes of hygienic status and overcrowding. A recent study in Turkey compared 2 neighboring villages with different socioeconomic status. The only factor that was statistically significantly related to pediculosis capitis was size of the household; >6 inhabitants was associated with increased prevalence (9). n nAnother parameter that may indirectly influence overall prevalence and account for the leveling of the prevalence gradient between rich and poor is awareness of head lice and preventive and therapeutic practices. A study in Australia showed that although parents prefer to play a major role in prevention and treatment, they may lack insight into recent advances and dilemmas regarding these measures (10). n nVariations in reported prevalence were found even in data from the same country. These differences can result from surveys being conducted during different seasons, various examination techniques, reporting of active infestation or presence of nits, and potential introduction of effective pediculicides. n nAlthough head lice account for a substantial number of missed schooldays in children, among others, it is surprising that pediculosis capitis is not monitored and prevalence is not regularly reported. Although we cannot extinguish the parasite, effective monitoring and planning will enable us to limit the prevalence and distribution of this parasitosis.

Socioeconomic status (SES) as a determinant of adherence to treatment in HIV infected patients: a systematic review of the literature

ObjectivesIt has been shown that socioeconomic status (SES) is associated with adherence to treatment of patients with several chronic diseases. However, there is a controversy regarding the impact of SES on adherence among patients with the human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). Thus, we sought to perform a systematic review of the evidence regarding the association of SES with adherence to treatment of patients with HIV/AIDS.MethodsWe searched the PubMed database to identify studies concerning SES and HIV/AIDS and collected data regarding the association between various determinants of SES (income, education, occupation) and adherence.FindingsWe initially identified 116 potentially relevant articles and reviewed in detail 17 original studies, which contained data that were helpful in evaluating the association between SES and adherence to treatment of patients with HIV/AIDS. No original research study has specifically focused on the possible association between SES and adherence to treatment of patients with HIV/AIDS. Among the reviewed studies that examined the impact of income and education on adherence to antiretroviral treatment, only half and less than a third, respectively, found a statistically significant association between these main determinants of SES and adherence of patients infected with HIV/AIDS.ConclusionOur systematic review of the available evidence does not provide conclusive support for existence of a clear association between SES and adherence among patients infected with HIV/AIDS. There seemed to be a positive trend among components of SES (income, education, occupation) and adherence to antiretroviral treatment in many of the reviewed studies, however most of the studies did not establish a statistically significant association between determinants of SES and adherence.

Mortality and morbidity of HIV infected patients receiving HAART: a cohort study.

HAART has substantially decreased mortality and morbidity among HIV-infected patients. We retrospectively analyzed morbidity and mortality in a cohort of HIV-infected adult patients with prolonged and frequent follow up (1987-2006). The study was divided in pre-HAART and HAART period for comparative reasons. In total, 615 HIV-infected patients (54 females) were included in our study. 144 died during the pre-HAART period (51.4 deaths per 100 patients). During the HAART period only 38 patients died from a total of 335 patients receiving HAART (11.3 deaths per 100 patients); the follow up in this part of the cohort was 2139 persons-years and the death incidence 1.77 deaths/per 100 person-years. The subanalysis excluding patients who died within 3 months from admission showed that death incidence among patients that have been receiving HAART from the time of diagnosis (1.2 deaths per 100 person-years) was slightly lower, compared to the death incidence of patients treated for some time with non-HAART as well (1.58 deaths per 100 persons-years). After the availability of HAART in this unit, the proportion of non-AIDS related deaths increased significantly from 8% to 40% (p<0.001); infections remained the leading cause of death in both groups of patients. Tauhe most common non-AIDS related causes of deaths were cancer and coronary disease. Our data from the studied cohort adds to the relevant literature regarding the dramatic reduction of morbidity and mortality that occurred after the availability of HAART.

Impact of Initial Discordant Treatment With β-Lactam Antibiotics on Clinical Outcomes in Adults With Pneumococcal Pneumonia: A Systematic Review

OBJECTIVEnTo systematically examine the available evidence regarding the effect of initial discordant therapy with beta-lactam antibiotics on mortality, clinical success, and bacteriological eradication in patients with pneumococcal pneumonia.nnnMETHODSnWe analyzed prospective studies that compared the clinical effectiveness of concordant (active in vitro) beta-lactam monotherapy with discordant (inactive in vitro) monotherapy with the same beta-lactam in patients with pneumococcal pneumonia. Relevant studies were identified from searches of the PubMed database (1950 to November 2005) and references from articles. Outcomes between groups of patients who received concordant and discordant treatment were compared by simple pooling of data and by estimation of pooled odds ratios or risk difference (RD), when applicable.nnnRESULTSnSix prospective studies were included in our analysis. No statistically significant difference was found in mortality of patients treated with beta-Iactam concordant and discordant therapy (51/275 [19%] vs 9/42 [21%]; P = .66; data from 6 studies; RD, -0.05; 95% confidence interval [CI], -0.23 to 0.12; data from 5 studies). In addition, no statistically significant difference was found regarding clinical success (37/42 [88%] vs 5/6 [83%]; P = .57; odds ratio, 2.57; 95% CI, 0.46 to 14.34; RD, 0.07; 95% CI, -0.36 to 0.50; data from 3 studies) or bacteriological success (24/30 [80%] vs 3/3 [100%]; P = .99; and RD, -0.18; 95% CI, -0.79 to 0.42; data from 2 studies) between concordant and discordant therapy.nnnCONCLUSIONnThe initial discordant treatment with beta-lactam antibiotics was not associated with a statistically significant Increase in mortality or clinical or bacteriological failure of therapy for pneumococcal pneumonia.

Multi-skeletal Pneumocystis jiroveci (carinii) in an HIV-seropositive patient.

We present our experience with skeletal involvement of Pneumocystis jiroveci (ex P. carinii) infection in an HIV-seropositive patient. The objective of this study was to alert clinicians to the possibility that extrapulmonary P. jiroveci could affect the skeletal system in HIV-infected patients with extremely rapid progression. P. jiroveci infection of skeletal system has been rarely described elsewhere. A 51-year-old man complained of fever for six weeks, cough, anorexia, fatigue, and chest pain. He was found to be HIV seropositive. Repetitive (six samples) sputum and bronchoalveolar lavage fluid microbiologic tests were negative. High-resolution chest computed tomography (CT) scan revealed a small pulmonary mass. Abdominal CT scan revealed lesions in liver, spleen, kidneys, adrenal glands, lumbar vertebrae, and sacrum. Brain and skull CT scan was normal. A fine-needle biopsy of the lung mass was unrevealing. Cytological examination of sputum specimens showed findings consistent with non-small-cell lung carcinoma. Nineteen weeks post-presentation, the patient reported low-back pain. Within 24 hours after the onset of low-back pain, he developed focal neurological deficits, and a magnetic resonance imaging (MRI) of the skull and spine showed osteolytic lesions of the temporal bones bilaterally, multiple vertebral lesions, and lesions of sacrum and iliac bones. Radiotherapy of the lumbar spine and pelvis was given. Sternal aspiration was performed. Cytological examination revealed P. jiroveci. In conclusion, we describe a rare case of disseminated P. jiroveci infection in an HIV-seropositive patient, with multiple skeletal lesions, especially in the skull and in vertebrae region, and concomitant non-small-cell lung cancer, with a very poor prognosis.

Prevalence of Genotypic Resistance to Nucleoside Analogues, Nonnucleoside Analogues, and Protease Inhibitors in HIV-Infected Persons in Athens, Greece

The objective was to study the prevalence of genotypic resistance to nucleoside analogues (NRTIs), nonnucleoside analogues (NNRTIs), and protease inhibitors among HIV-1-infected persons in Athens, Greece. Patients followed at two HIV units were examined for prevalence of emergence of antiretroviral resistance mutations (ARMs) in this observational study where complete therapy history was available. All mutations were recorded according to the October/November 2005 IAS-USA Drug Resistance Mutations Figures. A total of 234 patients underwent genotypic testing of 2069 followed (1987-2004). The most frequent ARMs of each drug category were to NRTIs at codons M184V [present in 149 tests (63.6%)], M41L [79 (33.8%)], K70R [66 (28.2%)], M184VI [58 (24.8%)], T215YF [53 (22.7%)], D67N [82 (35.0%)], T215Y [72 (30.8%)], K219Q [47 (20.1%)], K219E/Q [54 (23.1%)], and L210W [49 (20.9%)], respectively. The most prevalent mutations related to NNRTIs were K103N [present in 59 tests (25.2%)], G190A [50 (21.4%)], and Y181C [48 (20.5%]. Mutations in the protease gene showed that the ARM at residue L63P was the most prevalent present in 119 samples (50.9%). L90M (26.5%) was among the most frequently observed single key protease mutations in our series, although variables of V82 and I54 amino acid substitutions were more frequent. M184V (63.6%) and K103N (25.2%) were the most frequent mutations related to NRTIs and NNRTIs, respectively.

Hyperlactatemia due to Nevirapine

Background: Hyperlactatemia is a well-known adverse reaction in HIV-infected patients who are treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) (1). However, data on its association with the other 2 widely used classes of antiretroviral agents, nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors, are inconclusive. To our knowledge, no cases of hyperlactatemia secondary to nevirapine use have been reported to date. Objective: To describe a patient with nevirapine-induced hyperlactatemia who gradually recovered after cessation of treatment. Methods and Findings: A 36-year-old man received a diagnosis of HIV infection in November 2000 and began receiving azidothymidine-lamivudine-nevirapine in January 2001. He tolerated the treatment well for 20 months, achieving suppression of the viral load to undetectable levels and an increase in CD4 + cell count to 1.506 X 10 9 cells/L. He then began to report nausea, fatigue, dyspnea, and pain in the epigastrium. He did not take any other prescription or over-the-counter medication. On admission, he was slightly tachypneic (20 breaths/min), and physical examination was notable only for mild epigastric tenderness. Laboratory work-up showed mildly elevated aminotransferase levels (aspartate aminotransferase level, 44 U/L [normal range, 7 to 40 U/L]; alanine aminotransferase level, 64 U/L [normal range, 7 to 40 U/L]), elevated triglyceride level (3.03 mmol/L [268 mg/dL] [normal range, 0.57 to 1.69 mmol/L {50 to 150 mg/dL}]), elevated cholesterol level (8.21 mmol/L [317 mg/dL] [normal range, <4.92 mmol/L [<190 mg/dL}]), and a lactate level of 13.1 mmol/L (normal range, 0.6 to 2.4 mmol/L) with mild metabolic acidosis (pH level, 7.34; HCO 3 level, 18.3 mmol/L). Results of serologic tests for hepatitis B and C viruses were negative. An extensive investigation ruled out other pathologic conditions that could lead to hyperlactatemia. Empirical therapy consisted of withdrawal of the antiretrovirals and administration of L-carnitine and a multivitamin tablet containing thiamine and vitamin B 6 (2, 3). Three weeks later, the patient had marked clinical improvement and a gradual decrease in lactate level to 5 mmol/L. At this time, and because of an increase in viral load, nevirapine-saquinavir-ritonavir treatment was administered (eliminating the NRTIs azidothymidine and lamivudine) and the cofactors supplementation was continued. Six weeks later, symptoms recurred and were accompanied by an increase in lactate level to 12.1 mmol/L. Finally, the antiretroviral regimen was changed to saquinavir-lopinavir-ritonavir. The lactate level normalized (despite withdrawal of the vitamins), which persisted up to the last follow-up visit in December 2005. The Figure shows the progression of the lactate level over time and its association with the therapeutic interventions. Conclusions: We present what we believe is the first well-documented case of hyperlactatemia associated with the use of the NNRTI nevirapine. In fact, determination of Naranjo and colleagues probability scale (4) reveals a score of 9, indicating a highly probable adverse event.

Viral (HIV) Entry: How Does It Work?

HIV life (replication) cycle involves attachment and fusion of the HIV particle with host target cells to initiate the infectious cycle. Entry into the host cell results in conversion of the viral genes from an RNA form to a DNA form and integration of the viral genetic material into the chromosomes of the now infected cell, where it persists for the life of the host cell, resulting in replication and budding forming new virions that are released from the infected host cells.