Opioid Use and Chronic Infections: The Value of Addressing the Syndemic in Correctional Settings Via Telemedicine Guidance and Broader Use of Long-Acting Medications.

In the United States, we are experiencing linked epidemics (a syndemic) of substance use disorders (SUDs) and infections associated with drug use, including unsafe injecting and unsafe sex in exchange for drugs or money. Current drug laws, together with risk-taking behavior among persons with SUDs, contribute to disproportionately high prevalences of these conditions in correctional settings. Detection and treatment of diseases with a high impact on public health are best addressed in the settings where such conditions are most prevalent (ie, jails and prisons for SUDs and chronic infections). The effectiveness, safety, cost of care. and public health impact of these conditions can be improved by means of broader screening and expanded access to specialty consultations through telemedicine/telehealth, along with broader use of long-acting medications for the treatment of human immunodeficiency virus and SUDs. Expanding telemedicine/telehealth, first for specialties which do not require advanced technology (eg, infectious diseases, addictions), can eventually lead to further advancements in correctional healthcare.

Hantavirus Infection with Renal Failure and Proteinuria, Colorado, USA, 2019.

In North America, hantaviruses commonly cause hantavirus pulmonary syndrome (HPS). Clinical descriptions of hantavirus-associated renal disease in the Americas are scarce. Herein, we discuss the case of a 61-year-old man whose predominant manifestations were acute kidney injury and proteinuria. Clinical recognition of renal signs in hantavirus infections can reduce risk for death.

Severe acute Q fever pneumonia complicated by presumed persistent localized Q fever endocarditis in a renal transplant recipient: A case report and review of the literature.

Q fever in solid organ transplant (SOT) recipients is rarely described in the medical literature. We present a case of severe acute Q fever pneumonia that evolved into persistent localized Q fever endocarditis in a renal transplant recipient.

Cytomegalovirus myocarditis in solid organ transplant recipients: A case series and review of literature.

Cytomegalovirus (CMV) is a DNA virus of the Herpesviridae family and is estimated to affect 15%-30% of high-risk solid organ transplant recipients. Typical manifestations of CMV end-organ disease in this population include colitis, esophagitis, and pneumonitis, and myocarditis is a rarely reported manifestation. We describe two cases of CMV myocarditis in solid organ transplant recipients and review the literature regarding previously published cases of CMV myocarditis.

Access to Specialty Services: Opportunities for Expansion of Telemedicine to Support Correctional Health Care in Colorado.

Introduction: The United States has the largest correctional population in the world and many inmates lack access to timely health care. Studies have shown that telemedicine could improve the situation in a practical and cost-effective fashion. We aimed to evaluate currently established services as well as any potential need for expansion of telemedicine within correctional settings in Colorado. Methods: We designed a prospective survey-based pilot study using mixed methods research techniques. Results: Colorado has 50 county jails, 19 prisons, and 3 private prison facilities. Of these, 46 correctional facilities (45 jails and the state prison) were contacted. Twenty responded (19 jails and the prison) representing 43.5% response rate. Only 10% did not have on-site health care providers available at all, 31.6% were already using telemedicine for some of their needs, 52.9% were "very interested," 5.9% "somewhat interested," 17.6% "not so interested," and 23.5% were "not at all interested" in further information regarding telemedicine services. Discussion: Our study as well as current literature suggest that telemedicine could serve to fill in certain gaps of care within correctional populations, especially for over-represented conditions (i.e., chronic infectious diseases, such as HIV and hepatitis C virus, substance use disorders, or mental health disorders). Conclusions: There is enthusiasm but also certain amount of skepticism among Colorado's jail administrators with respect to the implementation, or even the cost-effectiveness potential of telemedicine. Telemedicine in these settings may require individualized approach and enough creative flexibility to allow for nimble adjustments based on the constraints and needs of individual institutions.

The variable presentations and broadening geographic distribution of hepatic fascioliasis.

We report 2 unrelated cases of hepatic fascioliasis in travelers returning to the United States from Africa and the Middle East. The first case presented with acute infection. Prominent clinical features included abdominal pain, elevated liver transaminases, serpiginous hepatic lesions, pericapsular hematoma, and marked peripheral eosinophilia. The second case was diagnosed in the chronic stage of infection and presented with right upper quadrant abdominal pain, cystic hepatic lesions, and an adult fluke in the common bile duct. We review the life cycle of Fasciola species, the corresponding clinical features during the stages of human infection, diagnostic methods, and the evolving understanding of the epidemiology of human fascioliasis, particularly emphasizing fascioliasis in African countries.

Enhancement of alkaline phytase production in Pichia pastoris: influence of gene dosage, sequence optimization and expression temperature.

Supplementation of animal feed with phytases has proven to be an effective strategy to alleviate phosphorous contamination of soil and water bodies. The inability of non-ruminant animals to digest phytates in corn and soybeans contributes to environmental contamination. Alkaline phytase from lily pollen (LlALP) exhibits unique catalytic and thermal stability properties that could be useful as a feed supplement. rLlALP2 was successfully expressed in Pichia pastoris; however, enzyme yields were modest (8-10 mg/L). In this paper, we describe our efforts to enhance rLlALP2 yield by investigating the influence of the following potential limiting factors: transgene copy number, codon bias, sequence optimization, and temperature during expression. Data presented indicate that increasing rLlAlp2 copy number was detrimental to heterologous expression, clones with one copy of wt-rLlAlp2 produced the highest activity, clones with two, four and seven or more copies produced 70%, 25% and 10% respectively, of enzyme activity implying that gene dosage is not limiting rLlALP2 yield. Use of a sequence-optimized rLlAlp2 increased the yield of the active enzyme by 25-50% in one/two copy clones, suggesting that translational efficiency is not a major bottleneck for rLlALP2 expression. Reducing the temperature during heterologous expression led to increases of 1.2-20-fold suggesting that protein folding and post-translational processes may be the dominant factors limiting rLlALP2 expression. Early knowledge of the transgene copy number allowed us to develop a more rational strategy for yield enhancement. Cumulatively, sequence optimization and temperature reduction led to the doubling of rLlALP2 enzyme activity in P. pastoris.

HIV and COVID-19: review of clinical course and outcomes.

Background:Understanding the relationship between HIV and SARS-CoV-2 has important public health implications.Objective:To summarize current research on COVID-19 among people with HIV (PWH) as published through 15 July 2021.Methods: We conducted a search of PubMed, Scopus, preprint databases (medRxiv, bioRxiv), and the references of publications found using key terms relevant to COVID-19 ('COVID-19' OR 'SARS-CoV-2' OR 'coronavirus') AND to HIV ('HIV' OR 'Human Immunodeficiency Virus' OR 'AIDS' OR 'Acquired Immunodeficiency Syndrome'). We summarized all articles that reported data or opinions on SARS-CoV-2 and HIV coinfection.Conclusions: Although many initial case series and cohort studies found no increased risk for SARS-CoV-2 infection or severe COVID-19 outcomes among PWH, recent studies have signaled an increased risk for severe COVID-19 disease progression even in the setting of well-controlled HIV. Whether this is due to the increased prevalence of comorbidities in PWH and other social determinants of health is unknown. These conflicting findings highlight the continued need for COVID-19 related research among PWH that addresses COVID-19 disease course as well as exacerbation of existing comorbidities already disproportionately represented among PWH.

Heterologous expression and functional characterization of a plant alkaline phytase in Pichia pastoris.

Phytases catalyze the sequential hydrolysis of phytic acid (myo-insositol hexakisphosphate), the most abundant inositol phosphate in cells. Phytic acid constitutes 3-5% of the dry weight of cereal grains and legumes such as corn and soybean. The high concentration of phytates in animal feed and the inability of non-ruminant animals such as swine and poultry to digest phytates leads to phosphate contamination of soil and water bodies. The supplementation of animal feed with phytases results in increased bioavailability to animals and decreased environmental contamination. Therefore, phytases are of great commercial importance. Phytases with a range of properties are needed to address the specific digestive needs of different animals. Alkaline phytase (LlALP1 and LlALP2) which possess unique catalytic properties that have the potential to be useful as feed and food supplement has been identified in lily pollen. Substantial quantities of alkaline phytase are needed for animal feed studies. In this paper, we report the heterologous expression of LlALP2 from lily pollen in Pichia pastoris. The expression of recombinant LlALP2 (rLlALP2) was optimized by varying the cDNA coding for LlALP2, host strain and growth conditions. The catalytic properties of recombinant LlALP2 were investigated extensively (substrate specificity, pH- and temperature dependence, and the effect of Ca(2+), EDTA and inhibitors) and found to be very similar to that of the native LlALP2 indicating that rLlALP2 from P. pastoris can serve as a potential source for structural and animal feed studies.

Intraoperative complications of LASIK flaps using the IntraLase femtosecond laser in 3009 cases.

PURPOSE: To report the incidence and management of intraoperative complications while using the IntraLase FS femtosecond laser (Abbott Medical Optics) for flap creation during LASIK. METHODS: A prospective log of intraoperative flap creation complications using the femtosecond laser was maintained over 3009 consecutive LASIK surgeries from August 2002 through July 2009. RESULTS: Eleven (0.37%) intraoperative complications occurred. Eight suction breaks occurred, seven of which were treated with reapplication of the laser, the other by completing the side-cut with surgical dissection. One case of incomplete flap creation was treated with surgical dissection. Two cases of adherent flap were treated with reapplication of laser energy and surgical dissection. All surgeries were completed successfully during the same operative session. CONCLUSIONS: Intraoperative complications during flap creation are minor, infrequent, and can be managed effectively within the same surgical session.

Routine opt-out rapid HIV screening and detection of HIV infection in emergency department patients.

CONTEXT: The Centers for Disease Control and Prevention (CDC) recommends routine (nontargeted) opt-out HIV screening in health care settings, including emergency departments (EDs), where the prevalence of undiagnosed infection is 0.1% or greater. The utility of this approach in EDs remains unknown. OBJECTIVE: To determine whether nontargeted opt-out rapid HIV screening in the ED was associated with identification of more patients with newly diagnosed HIV infection than physician-directed diagnostic rapid HIV testing. DESIGN, SETTING, AND PATIENTS: Quasi-experimental equivalent time-samples design in an urban public safety-net hospital with an approximate annual ED census of 55,000 patient visits. Patients were 16 years or older and capable of providing consent for rapid HIV testing. INTERVENTIONS: Nontargeted opt-out rapid HIV screening and physician-directed diagnostic rapid HIV testing alternated in sequential 4-month time intervals between April 15, 2007, and April 15, 2009. MAIN OUTCOME MEASURES: Number of patients with newly identified HIV infection and the association between nontargeted opt-out rapid HIV screening and identification of HIV infection. RESULTS: In the opt-out phase, of 28,043 eligible ED patients, 6933 patients (25%) completed HIV testing (6702 patients were screened; 231 patients were diagnostically tested). Ten of 6702 patients (0.15%; 95% CI, 0.07%-0.27%) who did not decline HIV screening in the opt-out phase had new HIV diagnoses, and 5 of 231 patients (2.2%; 95% CI, 0.7%-5.0%) who were diagnostically tested during the opt-out phase had new HIV diagnoses. In the diagnostic phase, of 29,925 eligible patients, 243 (0.8%) completed HIV testing. Of these, 4 patients (1.6%; 95% CI, 0.5%-4.2%) had new diagnoses. The prevalence of new HIV diagnoses in the opt-out phase (including those diagnostically tested) and in the diagnostic phase was 15 in 28,043 (0.05%; 95% CI, 0.03%-0.09%) and 4 in 29,925 (0.01%; 95% CI, 0.004%-0.03%), respectively. Nontargeted opt-out HIV screening was independently associated with new HIV diagnoses (risk ratio, 3.6; 95% CI, 1.2-10.8) when adjusting for patient demographics, insurance status, and whether diagnostic testing was performed in the opt-out phase. The median CD4 cell count for those with new HIV diagnoses in the opt-out phase (including those diagnostically tested) and in the diagnostic phase was 69/microL (IQR, 17-430) and 13/microL (IQR, 11-15) , respectively (P = .02). CONCLUSION: Nontargeted opt-out rapid HIV screening in the ED, vs diagnostic testing, was associated with identification of a modestly increased number of patients with new HIV diagnoses, most of whom were identified late in the course of disease.

Vaccination and Immunoprotection in People with HIV.

Vaccines play an important role in HIV primary care and are available for several sexually transmitted infections, including those caused by hepatitis A virus (HAV), hepatitis B virus (HBV), and human papillomavirus (HPV). HAV vaccination is increasingly important, given recent hepatitis A outbreaks and lack of immunity in many adults. A novel formulation of the hepatitis B vaccine shows promise in increasing rates of seroprotection. The Advisory Committee on Immunization Practices recommends the meningococcal conjugate vaccine for all individuals with HIV and has expanded the age range for administration of the HPV vaccine, recommending shared decision making about its administration in adults aged 27 to 45 years. This article summarizes a presentation by Steven C. Johnson, MD, at the International Antiviral Society-USA (IAS-USA) annual continuing education program held in New York, New York, in September 2019.

COVID-19 Serosurveillance May Facilitate Return-to-Work Decisions.

Public health measures are needed to resolve the novel coronavirus disease (COVID-19) pandemic, although a looming economic fallout merits close attention. Early safe reintroduction of immune individuals into the workforce may be essential to protecting the economic welfare of communities. Reverse transcriptase-polymerase chain reaction testing, our primary diagnostic tool to date, has sensitivity and timing concerns, owing to sampling/handling errors, as well as a complex virus-host interaction. Reverse transcriptase-polymerase chain reaction assays do not establish immune status once the virus has been cleared. Targeted serosurveillance for the determination of individuals' potential for transmissibility, particularly if paired with direct pathogen testing, may aid in "cleared for business" decision-making.

Lower Mortality Associated With Adjuvant Corticosteroid Therapy in Non-HIV-Infected Patients With Pneumocystis jirovecii Pneumonia: A Single-Institution Retrospective US Cohort Study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids in these patients is uncertain. This study aimed to determine if corticosteroids would reduce mortality in a cohort of HIV-negative PJP patients. METHODS: We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995 and 2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify mortality predictors. RESULTS: Common underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), and solid organ transplantation (10.7%). HIV-negative patients had higher rates and durations of mechanical ventilation and intensive care unit stay. Survival was significantly increased in HIV-negative patients receiving adjuvant corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (P = .034). In an adjusted multivariable model, no adjuvant corticosteroid use was associated with higher mortality (odds ratio, 13.5; 95% CI, 1.1-158.5; P = .039) regardless of HIV status. CONCLUSIONS: We found substantial mortality among HIV-negative patients with PJP, and adjuvant corticosteroid use was associated with decreased mortality. Response to corticosteroids is best established in HIV-infected patients, but emerging reports suggest a similar beneficial response in PJP patients without HIV infection. Further prospective studies may establish a more definitive role of the addition of corticosteroids among HIV-negative patients with PJP.

Examining Mortality to Identify Opportunities for Improved Care Among Adults with HIV in a Single Academic Medical Center.

Mortality for people living with HIV (PLWH) has dramatically decreased since the mid-1990s and the proportion of deaths attributable to non-AIDS-related conditions has increased. Deceased PLWH were identified from a single academic medical center through provider survey and electronic medical record query. Cause of death was determined using the Coding Causes of Death in HIV tool following review of available medical records. Chart review of comorbidities, demographics, laboratory values, and previous completion of screening tests for malignancies was conducted for deaths during the period of 2013-2017. The proportion of AIDS-related deaths decreased markedly between 1995 and 2017, while the proportion of deaths from non-AIDS malignancies increased. From 2013 to 2017, 30 of 121 deaths were attributed to AIDS-related conditions, 32 to non-AIDS malignancies, 14 to suicide/homicide or sudden death, 10 to cardiac causes, 28 to other non-HIV causes, and 7 to unknown causes. Those who died of non-AIDS-related malignancies were older than AIDS-related deaths [mean age 55.8 (7.6) vs. 47.3 (13.5), p value = .003]. Less than half of potentially eligible patients had documented colon cancer screening. The number of individuals dying from AIDS-related conditions has decreased significantly and non-AIDS-related causes, particularly non-AIDS-related malignancies, have become more prominent causes of death. As our patients age, a greater focus needs to be placed on management of comorbid illnesses and screening and prevention of malignancy.

Lily pollen alkaline phytase is a histidine phosphatase similar to mammalian multiple inositol polyphosphate phosphatase (MINPP).

Phytic acid is the most abundant inositol phosphate in cells; it constitutes 1-5% of the dry weight of cereal grains and legumes. Phytases are the primary enzymes responsible for the hydrolysis of phytic acid and thus play important roles in inositol phosphate metabolism. A novel alkaline phytase in lily pollen (LlALP) was recently purified in our laboratory. In this paper, we describe the cloning and characterization of LlALP cDNA from lily pollen. Two isoforms of alkaline phytase cDNAs, LlAlp1 and LlAlp2, which are 1467 and 1533 bp long and encode proteins of 487 and 511 amino acids, respectively, were identified. The deduced amino acid sequences contains the signature heptapeptide of histidine phosphatases, -RHGXRXP-, but shares < 25% identity to fungal histidine acid phytases. Phylogenetic analysis reveals that LlALP is most closely related to multiple inositol polyphosphate phosphatase (MINPP) from humans (25%) and rats (23%). mRNA corresponding to LlAlp1 and LlAlp2 were expressed in leaves, stem, petals and pollen grains. The expression profiles of LlAlp isoforms in anthers indicated that mRNA corresponding to both isoforms were present at all stages of flower development. The expression of LlAlp2 cDNA in Escherichia coli revealed the accumulation of the active enzyme in inclusion bodies and confirmed that the cDNA encodes an alkaline phytase. In summary, plant alkaline phytase is a member of the histidine phosphatase family that includes MINPP and exhibits properties distinct from bacterial and fungal phytases.

Antiretroviral Therapy for HIV Infection: When to Initiate Therapy, Which Regimen to Use, and How to Monitor Patients on Therapy.

Antiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START (Strategic Timing of Antiretroviral Treatment) trial, which showed a 57% reduction in risk for the composite end point of AIDS-related events, serious non-AIDS-related events, or death from any cause with immediate treatment in antiretroviral therapy-naive participants with CD4+ cell counts above 500/µL. Other changes in HIV care include the widespread adoption of integrase strand transfer inhibitor-based regimens. Considerations regarding when to initiate antiretroviral therapy, which initial regimens to use, and appropriate monitoring of individuals taking antiretroviral therapy are discussed. This article summarizes an IAS-USA continuing education webinar presented by Steven C. Johnson, MD, in July 2015.

Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection.

BACKGROUND: Maximum suppression of virus replication is often not achievable for persons infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). Available data suggest that lamivudine contributes to partial viral suppression, despite the presence of M184V mutations and high-level phenotypic lamivudine resistance. METHODS: Selective lamivudine withdrawal was studied in 6 subjects who had incomplete viral suppression during antiretroviral treatment for multidrug-resistant HIV-1 infection. RESULTS: Plasma levels of HIV-1 RNA increased to 0.5 log(10) copies/mL above baseline 6 weeks after the withdrawal of lamivudine treatment (P=.04), even though reversion of lamivudine resistance was not yet detected. Early increases in plasma levels of HIV-1 RNA after lamivudine withdrawal were associated with the presence of the T215Y/F mutation and broad phenotypic resistance to nucleoside reverse-transcriptase inhibitors at baseline. Genotypic and phenotypic reversion of lamivudine resistance was detected in 4 subjects 8-14 weeks after withdrawal of lamivudine therapy. The duration of lamivudine withdrawal ranged from 8 to 22 weeks; all subjects resumed lamivudine treatment. Plasma levels of HIV-1 RNA were 0.6 log(10) copies/mL above baseline (P=.03) when lamivudine therapy was resumed. After the resumption of lamivudine treatment, plasma HIV RNA levels decreased to baseline levels in 3 subjects but remained elevated in 3 subjects who had evolution of increased antiretroviral drug resistance during the period of lamivudine withdrawal. Safety concerns raised by this latter finding led to permanent closure of the study. CONCLUSIONS: In select cases of multidrug-resistant HIV-1 infection, lamivudine contributes to suppression of HIV-1 replication, despite the presence of M184V mutations and lamivudine resistance.