HIV Pre-exposure Prophylaxis Education for Clinicians Caring for Spanish-Speaking Men Who Have Sex With Men (MSM).

Introduction: A growing number of Liaison Committee on Medical Education-accredited allopathic medical schools offer formal bilingual (English and Spanish) medical education, and numerous other schools offer medical Spanish through elective workshops as part of their curricula. One significant health disparity in the Hispanic community is the incidence of HIV among Spanish-speaking men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) has emerged as an effective strategy to reduce the risk of HIV transmission. Methods: We developed an education module to train clinicians to discuss PrEP with Spanish-speaking MSM. Our module is adapted from an English module on PrEP education. It includes a Spanish-language PowerPoint slide deck with information about PrEP as well as a Spanish-language videotaped scripted clinical encounter. Results: The module was implemented on three occasions with 18 participants, and learners reported increased comfort in discussing and confidence in prescribing PrEP with Spanish-speaking patients. Discussion: This workshop can be incorporated within medical Spanish curriculums offered at health professional schools and community-based organizations dedicated to reducing the HIV burden in the Spanish-speaking Hispanic community.

Effect of Heat Exposure on Cognition in Persons with Tetraplegia.

Individuals with cervical spinal cord injury (SCI) have impaired thermoregulatory mechanisms attributed to interruption of motor, sensory, and autonomic neuropathways. To determine the effects of heat exposure on core body temperature (Tcore) and cognitive performance in persons with tetraplegia, 8 individuals with chronic tetraplegia (C3-C7, American Spinal Cord Injury Association Impairment Scale A-B) and 9 able-bodied controls were acclimated to 27°C at baseline (BL) before being exposed to 35°C for up to 120 min (Heat Challenge). Rectal temperature (Tcore), distal skin temperatures (Tskavg), sweat rate (QSavg), microvascular skin perfusion (LDFavg), and plasma norepinephrine (NE) were measured. Cognitive performance was assessed using Stroop Color and Word and Wechsler Adult Intelligence Scale-Fourth Edition Digit Span tests at BL and at the end of Heat Challenge. After Heat Challenge, Tcore increased 0.78 ± 0.18°C (p < 0.001) in tetraplegics after an average of 118 ± 5 min. Tcore did not change in controls after 120 min. The increase in QSavg was larger in controls than in tetraplegics (946 ± 672% vs. 51 ± 12%; p = 0.007, respectively). LDFavg increased only in controls (109 ± 93%; p = 0.008). Tskavg appeared to increase less in tetraplegics than in controls. Plasma NE levels remained lower in tetraplegics compared to controls after Heat Challenge (86 ± 64 vs. 297 ± 84 pg/mL, respectively; p < 0.001). Stroop Color, Interference, and WAIS-IV Sequence scores increased only in tetraplegics (19.4 ± 17.2%; p < 0.05, 8.3 ± 5.9%; p < 0.05, 29.1 ± 27.4%; p < 0.05, respectively). Dysfunctional thermoregulatory mechanisms in the tetraplegic group allowed Tcore to rise from subnormal levels to normothermia during heat exposure. Normothermia was associated with improvements in attention, working memory, and executive function.

Self-reported effects of cold temperature exposure in persons with tetraplegia.

OBJECTIVE: Cervical spinal cord injury (tetraplegia) is known to interrupt sympathetic vasculature control, thereby preventing shunting of blood from the periphery to central organs when exposed to cold temperatures. As a result, persons with tetraplegia are at risk to develop hypothermia. However, information regarding the discomfort experienced during the cooler months (late fall, winter, early spring) is overwhelmingly anecdotal. It is not known, with any certainty, how those with tetraplegia perceive cold and if discomfort in colder environments restricts them from performing activities that they routinely would perform. DESIGN: Prospective, two-group, self-report surveys. SETTING: VA Medical Center and Kessler Institute for Rehabilitation. PARTICIPANTS: Forty-four subjects with tetraplegia; 41 matched non-SCI controls. OUTCOME MEASURES: Tetraplegic and control groups responded "yes" or "no" when asked whether cold seasonal temperatures allowed comfort or negatively affected participation in routine activities. RESULTS: Percentage of responses of tetraplegia compared to controls was different as to whether they felt cold when others in the same room were comfortable (82 vs. 24%; χ2 = 28.2, P < 0.0001), felt comfortable outdoors (17 vs. 43%; χ2 = 6.8, P = 0.009), or whether cold negatively affected bathing routines (55 vs. 15%; χ2 = 14.8, P = 0.0001), keeping physician appointments (46 vs. 12%; χ2 = 11.3, P = 0.0008), thinking clearly (41 vs. 7%; χ2 = 12.9, P = 0.0003), and completing usual work duties (46 vs. 10%; χ2 = 13.3, P = 0.0003). CONCLUSION: Cold seasonal temperatures have a reported greater negative impact on personal comfort and ability to perform vital activities in persons with tetraplegia than that of non-SCI controls. These findings highlight the need to address thermoregulatory impairment in persons with tetraplegia.

Effect of Mild Cold Exposure on Cognition in Persons with Tetraplegia.

UNLABELLED: Persons with a cervical spinal cord injury (SCI) have impaired thermoregulatory mechanisms secondary to interrupted of motor, sensory, and sympathetic pathways. In this study, our primary aim was to determine the effect of cool temperature exposure on core body temperature (Tcore) and cognitive performance in persons with tetraplegia. Seven men with chronic tetraplegia (C3-C7, American Spinal Injury Association Impairment Scale [AIS] A-C) and seven able-bodied controls were exposed to 27°C temperature at baseline (BL) before being exposed to 18°C for ≤120 min (Cool Challenge). Rectal temperature (Tcore), distal skin temperatures (Tskavg), microvascular skin perfusion (LDFavg), and systolic blood pressure (SBP) were measured. Cognitive performance was assessed using Delayed Recall, Stroop Interference tests at the end of BL and Cool Challenge. After Cool Challenge, Tcore decreased -1.2±0.12°C (p<0.0001) in tetraplegics after an average of 109±15.9 min with no change in controls after 120 min. Tskavg declined in both groups, but decline was less in tetraplegics than in controls (-8.6±5.8% vs. -31.6±7.9%, respectively; p<0.0001). LDFavg declined only in controls (-72±17.9%; p<0.001). Plasma norepinephrine levels differed after Cool Challenge (tetraplegics vs. CONTROLS: 86±62 pg/mL vs. 832±431 pg/mL, respectively; p<0.01). SBP increased from BL to Cool Challenge only in controls (123±16 mm Hg to 149±17 mm Hg, respectively; p<0.01). Delayed Recall and Stroop Interference scores both declined in tetraplegics (-55±47.4%; p<0.05 and -3.9±3.8%; p<0.05, respectively), but not in controls. We conclude that persons with tetraplegia lack adequate thermoregulatory mechanisms to prevent downward drift in Tcore on exposure to cool temperatures. This decline in Tcore was associated with deterioration of working memory and executive function.

Hemodynamic effects of L-threo-3,4-dihydroxyphenylserine (Droxidopa) in hypotensive individuals with spinal cord injury.

OBJECTIVES: To determine the effect of an escalating dose of droxidopa (100, 200, and 400 mg) compared with placebo on seated blood pressure (BP) in hypotensive individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effect of droxidopa on (1) supine BP and heart rate, (2) the change in BP and heart rate when these individuals were transferred from the supine to the seated position, and (3) adverse event (AE) reporting. DESIGN: Open-label dose titration trial. SETTING: A Veterans Administration Medical Center. PARTICIPANTS: Participants with SCI (C3-T12) (N=10) were studied during 4 laboratory visits. Subjects visited the laboratory for about 5 hours on each visit, which incorporated a 30-minute seated baseline, a 30- to 60-minute supine, and a 4-hour seated postdrug observation. INTERVENTIONS: Placebo on visit 1, droxidopa 100 mg on visit 2, droxidopa 200 mg on visit 3, and droxidopa 400 mg on visit 4. MAIN OUTCOME MEASURES: BP and heart rate changes from baseline to the postdrug period, orthostatic heart rate and BP responses, and subjective AE reporting. RESULTS: Seated BP was significantly elevated with 400 mg droxidopa compared with placebo and 100 mg droxidopa for 3 hours and was elevated for 2 hours compared with 200 mg droxidopa. Increase in supine BP was not worsened following droxidopa, and the expected fall in BP when transferred to the seated position was prevented with droxidopa 200 and 400 mg. There were no significant differences in the heart rate response or AE reporting among the study visits. CONCLUSIONS: Our preliminary findings suggest that droxidopa, at the doses tested, does not cause excessive increases in supine BP and the 400-mg dose appears to be effective at increasing seated BP for up to 3 hours in persons with SCI.

Systemic and cerebral hemodynamics during cognitive testing.

OBJECTIVE: Cognitive deficits are reported in 10-60% of individuals with SCI, the primary etiology of these deficits is believed to be concomitant traumatic brain injury (TBI). We recently documented diminished memory and marginally deficient attention and processing speed in individuals with SCI discordant for hypotension but matched for TBI. METHODS: Twenty-nine individuals participated: 16 non-SCI controls, 6 paraplegic (T2-T10) and 7 tetraplegic (C4-C8). The Stroop test was used to measure cognitive function and transcranial Doppler ultrasound was used to measure cerebral blood flow (CBF) while resting (5 min) and continuously during cognitive testing. Mean arterial pressure (MAP) was calculated from three brachial blood pressures and cerebral vascular resistance index was calculated as: CVRi = MAP/CBF. RESULTS: The paraplegia group (54 ± 6) was marginally older than the non-SCI (42 ± 15; p = 0.06) and tetraplegic (42 ± 11; p = 0.09) groups. Compared to non-SCI group, normalized t-score on the Stroop Color (SC) task was significantly lower in the paraplegic group (p < 0.05). In the tetraplegic group, MAP was significantly lower (p < 0.05) than the non-SCI and paraplegic groups, and related to SC t-score (r (2) = 0.873; p < 0.01). In the paraplegic group, CBF was reduced (p < 0.05) and CVRi increased (p < 0.05) compared to the non-SCI group, and CVRi was increased compared to the tetraplegic group (p < 0.05). A significant inverse relationship was noted between change in CVRi and SC t-score in the non-SCI group. CONCLUSION: Asymptomatic hypotension relates to cognitive performance in persons with tetraplegia; therefore, BP normalization should be considered. The inappropriate cerebral vascular response to cognitive testing and poor test performance should be investigated in persons with paraplegia.

Comparison of 24-hour cardiovascular and autonomic function in paraplegia, tetraplegia, and control groups: implications for cardiovascular risk.

BACKGROUND: Fluctuations in 24-hour cardiovascular hemodynamics, specifically heart rate (HR) and blood pressure (BP), are thought to reflect autonomic nervous system (ANS) activity. Persons with spinal cord injury (SCI) represent a model of ANS dysfunction, which may affect 24-hour hemodynamics and predispose these individuals to increased cardiovascular disease risk. OBJECTIVE: To determine 24-hour cardiovascular and ANS function among individuals with tetraplegia (n=20; TETRA: C4-C8), high paraplegia (n=10; HP: T2-T5), low paraplegia (n=9; LP: T7-T12), and non-SCI controls (n=10). Twenty-four-hour ANS function was assessed by time domain parameters of heart rate variability (HRV); the standard deviation of the 5-minute average R-R intervals (SDANN; milliseconds/ms), and the root-mean square of the standard deviation of the R-R intervals (rMSSD; ms). Subjects wore 24-hour ambulatory monitors to record HR, HRV, and BP. Mixed analysis of variance (ANOVA) revealed significantly lower 24-hour BP in the tetraplegic group; however, BP did not differ between the HP, LP, and control groups. Mixed ANOVA suggested significantly elevated 24-hour HR in the HP and LP groups compared to the TETRA and control groups (P<0.05); daytime HR was higher in both paraplegic groups compared to the TETRA and control groups (P<0.01) and nighttime HR was significantly elevated in the LP group compared to the TETRA and control groups (P<0.01). Twenty-four-hour SDANN was significantly increased in the HP group compared to the LP and TETRA groups (P<0.05) and rMSSD was significantly lower in the LP compared to the other three groups (P<0.05). Elevated 24-hour HR in persons with paraplegia, in concert with altered HRV dynamics, may impart significant adverse cardiovascular consequences, which are currently unappreciated.

Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia.

OBJECTIVE: To compare responses to head-up tilt (HUT) in individuals with chronic tetraplegia after midodrine hydrochloride (10 mg) versus nitro-L-arginine methyl ester (L-NAME, 1 mg/kg) administration. DESIGN: Prospective comparative drug trial. SETTING: Veterans Affairs medical center. PARTICIPANTS: Participants (N=7) were studied during 3 laboratory visits: no drug, midodrine (administered orally 30 min before HUT), and L-NAME (infused over a 60-min period). INTERVENTIONS: Anti-hypotensive agents, midodrine, and L-NAME. MAIN OUTCOME MEASURES: Mean arterial pressure (MAP), cerebral blood flow (CBF), and markers of the renin-angiotensin-aldosterone system (RAAS, plasma renin and serum aldosterone) were measured in the supine position at baseline (BL) and during a 45° HUT maneuver. Data were compared between BL and the average of 3 assessments collected during HUT. RESULTS: Orthostatic MAP and CBF were increased with the midodrine and L-NAME groups compared with the no drug trial and the relationship between the change in MAP and CBF was significant (r=0.770; P<0.001). Both L-NAME and midodrine appeared to suppress the post-HUT RAAS response compared with no drug. CONCLUSIONS: Increasing orthostatic blood pressure with L-NAME or midodrine appears to increase CBF and suppress the RAAS during HUT in persons with tetraplegia, although more data are needed to confirm these preliminary findings.

Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia.

OBJECTIVE: To determine the mean arterial pressure (MAP) and middle cerebral artery mean blood flow velocity (MFV) responses to 5 and 10mg midodrine during head-up tilt (HUT) in persons with tetraplegia. DESIGN: Prospective dose-response trial. SETTING: James J. Peters Veterans Administration Medical Center. PARTICIPANTS: Persons (N=10) with chronic tetraplegia (duration of injury=23+/-11 y). INTERVENTION: A dose titration study was performed over 3 testing days: control (no drug), 5mg midodrine (5mg), or 10mg midodrine (10mg) during 30 minutes of baseline (predrug/no drug), 30 minutes of supine rest postdrug/no drug, 15 minutes of progressive HUT (5 minutes at 15 degrees , 25 degrees , 35 degrees ), and 45 minutes of 45 degrees HUT. MAIN OUTCOME MEASURES: MAP and MFV response to midodrine supine and during HUT. RESULTS: Ten milligrams of midodrine significantly increased MAP while supine and during the HUT maneuver. Of note, the mean increase in MAP during HUT with 10mg was a result of a robust effect in 2 persons, with minimal change in the remaining 8 study subjects. The reduction in cerebral MFV during HUT was attenuated with 10mg. CONCLUSIONS: These findings suggest that midodrine 10mg may be efficacious for treatment of hypotension and orthostatic hypotension in select persons with tetraplegia. Although midodrine is routinely prescribed to treat orthostatic hypotension, the results of our work suggests limited efficacy of this agent, but additional studies in a larger sample of subjects with spinal cord injury should be performed.

Cognitive performance in hypotensive persons with spinal cord injury.

BACKGROUND: Due to sympathetic de-centralization, individuals with spinal cord injury (SCI), especially those with tetraplegia, often present with hypotension, worsened with upright posture. Several investigations in the non-SCI population have noted a relationship between chronic hypotension and deficits in memory, attention and processing speed and delayed reaction times. OBJECTIVE: To determine cognitive function in persons with SCI who were normotensive or hypotensive over a 24-h observation period while maintaining their routine activities. METHODS: Subjects included 20 individuals with chronic SCI (2-39 years), 13 with tetraplegia (C4-8) and 7 with paraplegia (T2-11). Individuals with hypotension were defined as having a mean 24-h systolic blood pressure (SBP) below 110 mmHg for males and 100 mmHg for females, and having spent >or=50% of the total time below these gender-specific thresholds. The cognitive battery used included assessment of memory (CVLT), attention and processing speed (Digit Span, Stroop word and color and Oral Trails A), language (COWAT) and executive function (Oral Trails B and Stroop color-word). RESULTS: Demographic parameters did not differ among the hypotensive and normotensive groups; the proportion of individuals with tetraplegia (82%) was higher in the hypotensive group. Memory was significantly impaired (P < 0.05) and there was a trend toward slowed attention and processing speed (P < 0.06) in the hypotensive compared to the normotensive group. INTERPRETATION: These preliminary data suggest that chronic hypotension in persons with SCI is associated with deficits in memory and possibly attention and processing speed, as previously reported in the non-SCI population.

The QT variability index and cardiac autonomic modulation: perspectives from apparently healthy men with spinal cord injury.

OBJECTIVE: To describe the effect of spinal cord injury (SCI) on the QT variability index (QTVI). METHODS: Digital electrocardiograms from 113 age-matched men (40 with tetraplegia, 26 with high paraplegia, 17 low paraplegia and 31 controls) were analyzed. RR interval, heart rate (HR) variability [total power (TP(RR)), low frequency (LF(RR)) and high frequency (HF(RR))], QT interval duration, Bazett HR-corrected QT (QTc), QT interval variance (QTVN) and QTVI were compared. RESULTS: Significant group main effects were present for RR, QTc, TP(RR) and LF(RR), but not QT duration, QTVN or HF(RR). Post hoc comparisons revealed the following: (1) longer RR in controls versus subjects with high paraplegia and low paraplegia, and in subjects with tetraplegia versus high paraplegia and low paraplegia; (2) QTc was longer in subjects with low paraplegia versus controls and shorter in subjects with tetraplegia versus high paraplegia, and (3) TP(RR) and LF(RR) were different in controls and subjects with high paraplegia compared to those with low paraplegia. QTVI was significantly elevated in all SCI groups compared to controls. Significant negative correlations between QTVI and HF(RR) were observed in all SCI groups, and TP(RR) and LF(RR) in subjects with tetraplegia and high paraplegia only. Age was negatively correlated in controls. CONCLUSIONS: QTVI is negatively affected in otherwise healthy SCI men compared to age-matched controls. This observation appears to reflect the attenuation of vagal modulation, sympathetic impairment above the sixth thoracic vertebra and/or a heightened degree of cardiovascular disease risk.

Exhaled nitric oxide levels are elevated in persons with tetraplegia and comparable to that in mild asthmatics.

The role of airway inflammation in mediating airflow obstruction in persons with chronic traumatic tetraplegia is unknown. Measurement of the fraction of exhaled nitric oxide (FeNO) affords a validated noninvasive technique for gauging the airway inflammatory response in asthma, although it has never been assessed in persons with tetraplegia. This study was designed to determine the FeNO in individuals with chronic tetraplegia compared with that in patients with mild asthma and healthy able-bodied individuals. Nine subjects with chronic tetraplegia, seven subjects with mild asthma, and seven matched healthy able-bodied controls were included in this prospective, observational, pilot study. All subjects were nonsmokers and clinically stable at the time of study. Spirometry was performed on all participants at baseline. FENO was determined online by a commercially available closed circuit, chemiluminescence method, using a single-breath technique. Subjects with tetraplegia had significantly higher values of FeNO than controls (17.72 +/- 3.9 ppb vs. 10.37 +/- 4.9 ppb; P < or = 0.01), as did subjects with asthma (20.23 +/- 4.64 ppb vs. 10.37 +/- 4.9 ppb, P < or = 0.001). There was no significant difference in FeNO between subjects with tetraplegia and those with asthma (17.72 +/- 3.9 ppb vs. 20.23 +/- 4.64 ppb, P < or = 0.27). Individuals with chronic tetraplegia have FeNO levels that are comparable to that seen in mild asthmatics and higher than that in healthy able-bodied controls. The clinical relevance of this observation has yet to be determined.

Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia.

OBJECTIVES: To determine the effects of 1.0 mg/kg nitro-L-arginine methyl ester (L-NAME) on orthostatic mean arterial pressure (MAP), serum aldosterone, and plasma renin concentrations in persons with chronic tetraplegia compared with nonspinal cord-injured controls. DESIGN: Prospective placebo-controlled intervention study. SETTING: James J. Peters Veterans Affairs Medical Center. PARTICIPANTS: Patients (n=5) with tetraplegia and controls (n=7) participated. The groups were matched for age, height, and weight; the average duration of injury in the tetraplegia group was 22+/-14 years. INTERVENTION: Subjects with tetraplegia visited the laboratory twice, receiving placebo on day 1 and L-NAME (1.0 mg/kg) on day 2. The agents were infused via an intravenous catheter over 60 minutes with the patient in the supine position. Data were collected during the infusion and then during head-up tilt to 45 degrees for 30 minutes. Control subjects visited the laboratory once for placebo infusion and the head-up tilt maneuver. MAIN OUTCOME MEASURE: Orthostatic MAP. RESULTS: Orthostatic MAP was reduced after placebo infusion in subjects with tetraplegia compared with controls (69+/-11 vs 89+/-9 mmHg, respectively; P<.01) and compared with L-NAME infusion (90+/-16 mmHg; P<.01). Orthostatic MAP did not differ when comparing the tetraplegia group with controls after L-NAME infusion. Orthostatic aldosterone levels were increased after placebo compared with L-NAME infusion in persons with tetraplegia; plasma renin levels did not differ among the groups. CONCLUSIONS: These data suggest that nitric oxide synthase inhibition may have clinical potential for treatment of orthostatic hypotension in persons with chronic tetraplegia.

Effect of hypotensive challenge on systemic hemodynamics and cerebral blood flow in persons with tetraplegia.

INTRODUCTION: Individuals with tetraplegia have impaired central control of sympathetic vascular modulation and blood pressure (BP); how this impairment affects cerebral blood flow (CBF) is unclear. OBJECTIVES: To determine if persons with tetraplegia maintain CBF similarly to able-bodied controls after a hypotensive challenge. METHODS: Seven individuals with chronic tetraplegia and seven age-matched, non-SCI control subjects underwent a hypotensive challenge consisting of angiotensin-converting enzyme (ACE) inhibition (1.25 mg enalaprilat) and 45 degrees head-up tilt (HUT). Heart rate (HR), low frequency systolic BP variability (LFsbp), brachial mean arterial pressure (MAP) and middle cerebral artery CBF were measured before and after the challenge. Group differences for the baseline (BL) to post-challenge response were determined by repeated measures ANOVA. RESULTS: HR did not differ between the groups in response to the hypotensive challenge. LFsbp response was significantly reduced in the tetra compared to the control group (-38 +/- 51 vs. 72 +/- 93%, respectively). MAP did not differ between the groups at BL but was significantly lower in the tetra compared to the control group post-challenge (55 +/- 13 vs. 71 +/- 9 mmHg, respectively); the percent change in MAP was significantly greater in the tetra than in the control group (-29 +/- 14.1 vs. -13 +/- 9%, respectively). However, CBF did not differ between the groups at baseline or post-challenge; the percent change in CBF post-challenge was not different between the tetra and control groups (-29 +/- 13.2 vs. -23 +/- 10.3%, respectively). INTERPRETATION: Despite impaired sympathetic vasomotor and BP control, CBF in persons with tetraplegia was comparable to that of control subjects during a hypotensive challenge.