A missing perspective: injectable pre-exposure prophylaxis for people who inject drugs.

The efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention has been established among people who inject drugs (PWID). HIV uninfected, at risk PWID, could likely benefit from long-acting injectable formulations of PrEP ("LAI-PrEP"); however, its acceptability in this population has not been previously documented. Thirty-three HIV-uninfected PWID in the U.S. Northeast completed an in-depth interview regarding perceived acceptability of LAI-PrEP. Coded data were synthesized using deductive thematic analysis. The majority of PWID interviewed believed LAI-PrEP would be acceptable. Participants perceived that receiving injections every two months would reduce barriers to daily oral PrEP adherence, including forgetting while "high" and safeguarding pills when homeless. A few participants expressed concerns regarding LAI-PrEP, including medical mistrust, a concern that injections could alter their "high" or be "triggering" for PWID. LAI-PrEP has the potential to reduce HIV among PWID; however, their perspectives are largely absent from research examining its efficacy, representing a missed opportunity.

Perspectives on HIV pre-exposure prophylaxis (PrEP) utilization and related intervention needs among people who inject drugs.

BACKGROUND: Antiretroviral pre-exposure prophylaxis (PrEP) is clinically efficacious and recommended for HIV prevention among people who inject drugs (PWID), but uptake remains low and intervention needs are understudied. To inform the development of PrEP interventions for PWID, we conducted a qualitative study in the Northeastern USA, a region where recent clusters of new HIV infections have been attributed to injection drug use. METHODS: We conducted qualitative interviews with 33 HIV-uninfected PWID (hereafter, "participants") and 12 clinical and social service providers (professional "key informants") in Boston, MA, and Providence, RI, in 2017. Trained interviewers used semi-structured interviews to explore PrEP acceptability and perceived barriers to use. Thematic analysis of coded data identified multilevel barriers to PrEP use among PWID and related intervention strategies. RESULTS: Among PWID participants (n = 33, 55% male), interest in PrEP was high, but both participants and professional key informants (n = 12) described barriers to PrEP utilization that occurred at one or more socioecological levels. Individual-level barriers included low PrEP knowledge and limited HIV risk perception, concerns about PrEP side effects, and competing health priorities and needs due to drug use and dependence. Interpersonal-level barriers included negative experiences with healthcare providers and HIV-related stigma within social networks. Clinical barriers included poor infrastructure and capacity for PrEP delivery to PWID, and structural barriers related to homelessness, criminal justice system involvement, and lack of money or identification to get prescriptions. Participants and key informants provided some suggestions for strategies to address these multilevel barriers and better facilitate PrEP delivery to PWID. CONCLUSIONS: In addition to some of the facilitators of PrEP use identified by participants and key informants, we drew on our key findings and behavioral change theory to propose additional intervention targets. In particular, to help address the multilevel barriers to PrEP uptake and adherence, we discuss ways that interventions could target information, self-regulation and self-efficacy, social support, and environmental change. PrEP is clinically efficacious and has been recommended for PWID; thus, development and testing of strategies to improve PrEP delivery to this high-risk and socially marginalized population are needed.

Early versus late tube feeding initiation after PEG tube placement: Does time to feeding matter?

BACKGROUND: Variation exists in the timing of tube feed initiation after percutaneous endoscopic gastrostomy (PEG) tube placement. The aim of our study was to review outcomes of early tube feed (ETF) versus late tube feed (LTF) initiation after PEG tube placement. METHODS: We performed a retrospective review of all trauma patients who underwent PEG tube placement from 1/2014 to 12/2018. ETF was defined as initiation < 24 h and LTF > 24 h after placement. The primary outcome measure was feeding intolerance and secondary outcomes included post-operative complications. All statistical analyses were performed using standard statistical methods (e.g. Pearson's Chi-squared, Fisher's exact and Mann Whitney-U tests). RESULTS: There were 295 patients (164 ETF and 131 LTF) that received a PEG tube at our level 1 trauma center. There was no difference with feeding intolerance at 12 h (5% vs. 4%; p = 0.88), 24 h (1% vs. 2%; p = 1.00), and 48 h (4% vs. 4%; p = 1.00). There was no difference when comparing intolerance symptoms such as nausea and vomiting (1% vs. 2%; p = 0.79), abdominal tenderness (2% vs. 3%; p = 0.76), high gastric residuals (2% vs. 2%; p = 1.00) and aspiration (0% vs. 2%; p = 0.39). There was no difference when comparing post-operative complications (4% vs. 8%; p = 0.21). CONCLUSIONS: Early tube feeding after PEG placement is safe and equivalent to late tube feeding in the adult trauma population. Future prospective studies are warranted to establish the optimal timing for initiation of tube feeds after PEG tube placement.

Implementing harm reduction in non-urban communities affected by opioids and polysubstance use: A qualitative study exploring challenges and mitigating strategies.

BACKGROUND: Harm reduction services, which typically provide overdose education and prevention with distribution of naloxone and other supplies related to safer drug use, help reduce opioid-related overdose and infectious disease transmission. However, structural stigma and the ongoing criminalization of drug use have limited the expansion of harm reduction services into many non-urban communities in the United States that have been increasingly affected by the health consequences of opioid and polysubstance use. METHODS: We conducted qualitative interviews with 22 professionals working with people who use drugs in cities and towns across Rhode Island and Massachusetts to understand challenges and strategies for engaging communities in accepting harm reduction perspectives and services. RESULTS: Our thematic analysis identified several interrelated challenges to implementing harm reduction services in non-urban communities, including: (1) limited understandings of harm reduction practice and preferential focus on substance use treatment and primary prevention, (2) community-level stigma against people who use drugs as well as the agencies supporting them, (3) data reporting and aggregating leading to inaccurate perceptions about local patterns of substance use and related health consequences, and (4) a "prosecutorial mindset" against drug use and harm reduction. From key informants' narratives, we also identified specific strategies that communities could use to address these challenges, including: (1) identifying local champions to advocate for harm reduction strategies, (2) proactively educating communities about harm reduction approaches before they are implemented, (3) improving the visibility of harm reduction services within communities, and (4) obtaining "buy-in" from a wide range of local stakeholders including law enforcement and local government. CONCLUSION: These findings carry important implications for expanding harm reduction services, including syringe service programs and safe injection sites, into non-urban communities that have a demonstrated need for evidence-based interventions to reduce drug-related overdose and infectious disease transmission.

Cocaine self-administration in rats with histories of cocaine exposure and discrimination.

RATIONALE: Interrelationships between the discriminative stimulus and reinforcing properties of psychoactive drugs and the way in which they may interact to control drug intake are unclear. Studies have shown that drug history can influence the expression of drug-produced behavioral effects. OBJECTIVE: The present study examined the acquisition and maintenance of intravenous cocaine self-administration in rats with a history of drug discrimination. METHODS: Two groups of male hooded rats (n=12 each) were successfully trained in a single-lever food-reinforced procedure to discriminate cocaine (10 mg/kg) from saline. Control groups (n=12 each) received drug injections and/or saline injections only and lever-pressed for food reinforcers with no discrimination training. Subsequently, all subjects were implanted with chronic jugular catheters and allowed to nose-poke for infusions of cocaine (0.2 mg/kg per infusion). RESULTS: Initial rates of responding were similar for all groups. Acquisition of self-administration on a FR-10 schedule of drug delivery was significantly faster for cocaine-exposed rats in comparison to all other groups (P<0.02). There were no differences between groups in the breaking points of cocaine and saline on a progressive ratio schedule of self-administration. Dose-response functions were obtained by two methods and were similar for all groups. CONCLUSION: These results are consistent with earlier studies demonstrating weakly sensitized primary reinforcing properties of cocaine in preexposed rats. Previous learning to discriminate cocaine impaired this sensitization.

Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy.

OBJECTIVE: To determine the predictive value of plasma HIV RNA and CD4 lymphocytes for HIV-associated dementia and sensory neuropathy. METHODS: A total of 1,604 AIDS-free HIV seropositive men from the Multicenter AIDS Cohort Study were followed over a 10-year period (1985 to 1995). HIV-associated dementia and sensory neuropathy were diagnosed according to standard definitions. Baseline samples were used to measure plasma HIV RNA levels with a branched DNA assay and levels of beta2-microglobulin, CD4 lymphocyte counts, and hemoglobin levels. RESULTS: Seventy-seven patients with HIV-associated dementia and 213 patients with sensory neuropathy were identified. Baseline HIV RNA levels above 3,000 copies/mL and CD4 counts below 500 cells/mm3 were predictive of both neurologic outcomes, but neither hemoglobin, body mass index, nor beta2-microglobulin were independently predictive. After adjusting for age and level of education, individuals with baseline plasma HIV RNA >30,000 copies/mL had a relative hazard for dementia 8.5 times (p < 0.001) that of those with <3,000 copies/mL, and those with CD4 counts <200 cells/mm3 had a 3.5-fold (p = 0.003) greater hazard relative to those with CD4 counts >500 cells/mm3. Individuals with HIV RNA >10,000 copies/mL had a 2.3-fold (p = 0.008) greater hazard of sensory neuropathy than those with <500 copies/mL, and men with <750 CD4 cells/mm3 had a 1.4-fold (p = 0.03) greater hazard than those with >750 CD4 cells/mm3. CONCLUSIONS: High levels of systemic HIV replication may "drive" the initiation of neurologic disease; effective suppression of HIV may reduce the incidence of dementia and neuropathy. Levels of plasma HIV RNA and CD4 counts, determined before the initiation of antiretroviral therapy, were predictive of HIV-associated dementia and sensory neuropathy.

Effect of LFA-1beta antibody on leukocyte adherence in response to hemorrhagic shock in rats.

The activation and adherence of leukocytes to the venular endothelium are critical steps in the pathogenesis of generalized microvascular injury following hemorrhagic shock. Previous studies have shown that the integrins CD11/CD18 play a significant role in this interaction. The purpose of this study is to examine the efficacy of anti-LFA-1beta, an antibody to CD11a/CD18, in attenuating leukocyte adherence before, during, and after hemorrhagic shock. Following a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 min in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of the small intestines were examined to quantitate leukocyte adherence using intravital microscopy. In sham-operated rats (control), there was minimal to no leukocyte adherence throughout the experiment. Hemorrhagic shock resulted in significant leukocyte adherence during resuscitation (10.8 +/- 1.7 cells/100 microm, P < 0.01) when compared to control. Anti-LFA-1beta, when given before hemorrhagic shock, significantly attenuated leukocyte adherence during resuscitation (1.1 +/- 0.8, P < 0.01) when compared with hemorrhagic shock alone. This protective effect of anti-LFA-1beta on leukocyte adherence was even demonstrated when it was given during (1.6 +/- 0.3, P < 0.01) and 10 min after hemorrhagic shock (5.8 +/- 0.4, P < 0.05). These results suggest that anti-LFA-1beta may be of potential therapeutic benefit against microvascular injury caused by hemorrhagic shock.

Leukocyte adherence and sequestration following hemorrhagic shock and total ischemia in rats.

The pathogenesis of generalized microvascular injury following hemorrhagic shock and total ischemia appears to be dependent on leukocytes interacting with the venular endothelium. The purpose of this study was to compare leukocyte adherence and sequestration following hemorrhagic shock with that of total ischemia in the small bowel mesentery of rats. Leukocyte adherence and sequestration was measured by direct visualization in vivo using intravital microscopy. In addition, sequestration was also quantitated by measuring tissue levels of myeloperoxidase, a marker of leukocyte infiltration. Mean arterial blood pressure was decreased to 40 mm Hg for 30 min (hemorrhagic shock group). In the total ischemia group, both the superior and inferior mesenteric arteries were clamped for 30 min followed by reperfusion. Hemorrhagic shock (9.4+/-1.5 cell/100 microm) and total ischemia (8.3+/-3 cell/100 microm) caused a statistically significant increases in leukocyte adherence 60 min postinsult as compared with controls (.9+/-1.5 cell/100 microm). However, the increase in leukocyte adherence appeared earlier and to a greater degree initially following total ischemia. Leukocyte sequestration as measured by intravital microscopy was significant only after total ischemia [(24.6+/-1.7 cell/(100 microm)2; p<.01] and not hemorrhagic shock [3.4+/-.6 cell/(100 microm)2] versus controls [2.2+/-.2 cell/(100 microm)2]. This difference in sequestration was also confirmed by tissue levels of myeloperoxidase. The results of this study suggest that the microvascular response following hemorrhagic shock is different than that of total ischemia, and caution is warranted when extrapolating the experimental results of one to the other.

Role of herniography in the diagnosis of occult hernias.

Twenty-two patients with groin or incisional pain and normal physical examinations underwent herniography. Eight patients were found to have 11 unsuspected hernias. Seven were direct, two indirect, and two incisional. Six of nine groin hernias were recurrent. Exploration confirmed the herniographic findings in all patients. Follow-up evaluation of patients undergoing herniorrhaphy revealed resolution of symptoms. Ten of the 14 patients with normal herniograms were asymptomatic 3 months after herniography. In these 22 patients, herniography resulted in a savings of $31,000. We conclude that herniography is cost-effective and useful in patients with abdominal wall pain of obscure etiology.

The local effect of PAF on leukocyte adherence to small bowel mesenteric venules following intra-abdominal contamination.

We have previously demonstrated that intra-abdominal contamination increases neutrophil infiltration into the gastrointestinal tract. The purpose of our current study was twofold: 1) to determine if leukocyte adherence to the mesenteric microvasculature occurred by local peritoneal contamination or by systemic mechanisms; and 2) to assess the role of platelet activation factor (PAF) in this process. Rats underwent cecal ligation and puncture (CLP), and 4 h after the procedure we used intravital microscopy to visualize the mesenteric microcirculation. Cecal ligation and puncture increased leukocyte adherence (22.3+/-5.5 leukocytes/100 microm) vs. sham (2.3+/-0.9, P < 0.05). WEB-2086, a PAF receptor antagonist, prevented this increase (6.47+/-4.8, P < 0.05). To assess if leukocyte adherence was due to topical effects, we performed similar experiments with the small bowel exteriorized. In such cases, CLP did not increase leukocyte adherence (1.2+/-0.8 vs. 1.4+/-0.9). In addition, topical application of highly diluted fecal matter (1:1000) increased leukocyte adherence (4.8+/-1.2) vs. control (0.6+/-0.3, P < 0.05). Our study demonstrates that leukocyte adherence in the mesenteric microcirculation following intra-abdominal contamination is due to direct topical exposure to fecal matter, and it is mediated by PAF.

Tonsillar abscess.

This article presents seven cases of patients with tonsillar abscess formation and discusses the pathophysiology of intratonsillar abscess formation.

Pressure ulcers. Physical, supportive, and local aspects of management.

Pressure ulcers are a common and serious problem predominately among elderly persons who are confined to bed or chair. Additional factors associated with pressure ulcer development include cerebrovascular accident, impaired nutritional intake, urinary or fecal incontinence, hypoalbuminemia, and previous fracture. Implementation of preventive measures, such as an in-depth assessment for mobility, a pressure-relieving device combined with adequate repositioning, and thorough evaluation for nutritional status and urinary incontinence, significantly reduce pressure ulcer incidence. If the pressure ulcer is a partial thickness (stage II) wound, the causative factors are probably friction or moisture. If the ulcer is full thickness (stage III and IV), it is secondary to pressure or shearing forces. The development of wound infection is the most common complication in the management approach. Osteomyelitis is not an uncommon occurrence and must be initially ruled out in all full thickness pressure ulcers. Surgical debridement of necrotic tissue is necessary prior to further treatment and assessments. Antibiotic therapy is indicated only upon evidence of infection (cellulitis, osteomyelitis, leukocytosis, bandemia, or fever). Topical pharmacologic agents may be used to prevent or treat infection but must be carefully controlled to avoid such adverse effects as toxicity to the wound, allergic reaction, and development of resistant pathogens. Proper use of occlusive dressings increase patient comfort, enhance healing, decrease the possibility of infection, save time, and reduce costs. A patient presenting an ulcer that fails to improve or, because of its size, will take a great deal of time to heal should be evaluated for surgical closure.