Human Papillomavirus Persistence and Association With Recurrent Cervical Intraepithelial Neoplasia After Cryotherapy vs Loop Electrosurgical Excision Procedure Among HIV-Positive Women: A Secondary Analysis of a Randomized Clinical Trial.

IMPORTANCE: Persistence of cervical high-risk human papillomavirus (hrHPV) after treatment for cervical intraepithelial neoplasia grade 2 or higher (CIN2+) has not been compared between cryotherapy and loop electrosurgical excision procedure (LEEP) among HIV-positive women. OBJECTIVE: To evaluate whether cryotherapy or LEEP is more effective at clearing hrHPV and whether persistent hrHPV is associated with CIN2+ recurrence among HIV-positive women. DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of a randomized clinical trial conducted among women with HIV, hrHPV, and CIN2+ in Nairobi, Kenya. From June 2011 to September 2016, 354 HIV-positive women with CIN2+ disease had hrHPV cervical samples collected before and after treatment with cryotherapy or LEEP. Data were analyzed from September 2018 to January 2021. INTERVENTIONS: Women were randomized 1:1 to receive cryotherapy or LEEP and were followed up every 6 months for 24 months with hrHPV cervical swab and Papanicolaou test with confirmatory biopsy. MAIN OUTCOMES AND MEASURES: The main outcomes of this analysis were hrHPV positivity defined as having 1 of 12 hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and disease recurrence defined as CIN grade 2 or higher as determined with cervical biopsy. RESULTS: A total of 354 HIV-positive women with CIN2+ were included in the study; mean (SD) age was 37 (8) years in the cryotherapy arm and 38 (9) years in the LEEP arm. Baseline hrHPV prevalence was 90% (160 of 177) in the cryotherapy arm and 94% (166 of 177) in the LEEP arm (P = .24), and the most common hrHPV types detected were 16 (87 of 326 [27%]), 58 (87 of 326 [27%]), 35 (86 of 326 [26%]), 52 (66 of 326 [20%]), and 18 (56 of 325 [17%]). Over 24 months, clearance of hrHPV was significantly higher among those who underwent LEEP compared with cryotherapy (hazard ratio, 1.40; 95% CI, 1.03-1.90; P = .03). In multivariable analysis, hrHPV type-specific persistence at 12-month follow-up was significantly associated with CIN2+ recurrence from 12 months to 24 months (adjusted hazard ratio, 4.70; 95% CI, 2.47-8.95; P < .001). Performance of hrHPV testing at 12 months for recurrent CIN2+ was 93% sensitivity, 46% specificity, 38% positive predictive value, and 95% negative predictive value. CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, HIV-positive women who received LEEP were more likely to clear hrHPV infection compared with those undergoing cryotherapy, reinforcing the efficacy of LEEP in this population. Persistent hrHPV was significantly associated with recurrent CIN2+, suggesting that LEEP's benefits may be related in part to its ability to clear hrHPV infection. Screening for hrHPV infection after treatment among HIV-positive women may be used to rule out recurrent CIN disease given its high sensitivity and negative predictive value. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01298596.

Loop electrosurgical excision procedure (LEEP) plus top hat for HIV-infected women with endocervical intraepithelial neoplasia in Kenya.

OBJECTIVE: To determine the utility of detecting endocervical cervical intraepithelial neoplasia (CIN) 2+ with endocervical curettage (ECC) and treating with loop electrosurgical excision procedure (LEEP) plus top hat (+TH) among women with HIV. METHODS: Cytology was followed by coloscopy-directed biopsy if participants had HSIL or ASC-H and biopsy plus ECC if there were glandular cells present. CIN2/3 on ECC and/or inadequate colposcopy (ENL) was treated with LEEP+TH, while CIN2/3 on ectocervix (ECL) received LEEP alone. Recurrent CIN2+ were compared over a 2-year follow-up. RESULTS: Of 5330 participants, 160 underwent ECC, 98 were CIN2/3 on ECC, and 77 received LEEP+TH. ECC detected 15 (9%) more women with CIN2/3 than biopsy alone. Women were more likely to have ENL if they were older (≥45 vs <35 years) (adjusted relative risk [aRR] 2.14; P = 0.009) and on antiretroviral treatment longer (≥2 vs <2 years) (aRR 3.97; P < 0.001). Over the 2-year follow-up, 35 (29%) ENL had recurrent CIN2+ after TH compared to 19 (24%) ECL after LEEP (hazard ratio 1.32; 95% confidence interval 0.75-2.31; P = 0.338). CONCLUSION: Among HIV-infected women, adding ECC did not increase detection of pre-cancerous disease significantly and treatment with LEEP+TH for ENL was comparable to treatment with LEEP for ECL.

Effect of Cryotherapy vs Loop Electrosurgical Excision Procedure on Cervical Disease Recurrence Among Women With HIV and High-Grade Cervical Lesions in Kenya: A Randomized Clinical Trial.

Importance: The World Health Organization recommends cryotherapy or loop electrosurgical excision procedure (LEEP) for histologically confirmed cervical intraepithelial neoplasia (CIN) grade 2 or higher regardless of HIV status. Cryotherapy is more feasible in resource-limited settings but may be less effective for women living with HIV. Objective: To evaluate whether cryotherapy or LEEP is a more effective treatment for high-grade cervical lesions among women with HIV. Design, Setting, and Participants: Single-center randomized trial conducted among women with HIV and CIN grade 2 or 3. From June 2011 to September 2016, women with HIV in Kenya underwent cervical screening with Papanicolaou testing and confirmatory biopsy. The final date on which a study procedure was administered was September 7, 2016. Interventions: Women with HIV infection and CIN grade 2 or 3 were randomized 1:1 to receive cryotherapy (n = 200) or LEEP (n = 200) and were followed up every 6 months for 24 months with a Papanicolaou test and confirmatory biopsy. Main Outcome and Measures: The primary outcome was disease recurrence, defined as CIN grade 2 or higher on cervical biopsy, during the 24-month follow-up period. Results: Among 400 women who were randomized (median age, 37.4 [interquartile range, 31.9-43.8] years), 339 (85%) completed the trial. Over 2 years, 60 women (30%) randomized to cryotherapy had recurrent CIN grade 2 or higher vs 37 (19%) in the LEEP group (relative risk, 1.71 [95% CI, 1.12-2.65]; risk difference, 7.9% [95% CI, 1.9%-14.0%]; P = .01). Adverse events occurred in 40 women (45 events, including change in pathology and death due to other causes) in the cryotherapy group and in 30 women (38 events, including change in pathology and unrelated gynecological complications) in the LEEP group. Conclusions and Relevance: In this single-center study of women with HIV infection and CIN grade 2 or 3, treatment with LEEP compared with cryotherapy resulted in a significantly lower rate of cervical neoplasia recurrence over 24 months. Cost-effectiveness analysis is necessary to determine whether the additional benefit of LEEP represents an efficient use of the additional resources that would be required. Trial Registration: ClinicalTrials.gov Identifier: NCT01298596.

Adolescent age is an independent risk factor for abnormal spirometry among people living with HIV in Kenya.

OBJECTIVES: As life expectancy of people living with HIV (PLWH) improves in low-income and middle-income countries (LMICs), the spectrum of HIV-related pulmonary complications may reflect a greater burden of chronic lung diseases as in high-income countries. We determined whether the risk of abnormal spirometry was greater among adolescent compared with adult PLWH at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya, and evaluated the role of other cofactors for abnormal spirometry. DESIGN: We prospectively enrolled adolescent and adult PLWH for this cross-sectional study. METHODS: Data collection included standardized questionnaires, clinical assessment, and prebronchodilator and postbronchodilator spirometry. Adolescents additionally underwent noncontrast chest computed tomography. Multivariable logistic regression determined associations of adolescent age with abnormal spirometry, adjusting for cofactors. RESULTS: Of 427 PLWH, 21 (40%) adolescents and 64 (17%) adults had abnormal spirometry. Among adolescents, 80% had abnormal chest CTs, and 79% had at least one respiratory symptom. Adolescent age (adjusted odds ratio 3.22; 95% confidence interval 1.48-6.98) was independently associated with abnormal spirometry, adjusting for recent CD4, HIV clinical stage, low BMI, indoor kerosene use, smoking pack-years, and prior pulmonary tuberculosis. Additional important cofactors for abnormal spirometry included prior pulmonary tuberculosis (3.15; 1.70-5.58), kerosene use (1.77; 1.04-3.04) and smoking pack-years (1.05; 1.00-1.10). Adolescent age, prior pulmonary tuberculosis, and smoking pack-years were significantly associated with airflow limitation. CONCLUSION: Adolescent age was independently associated with increased risk of abnormal spirometry, particularly airflow limitation. Studies to improve prevention, detection, and management of chronic lung disease across the lifespan among PLWH are needed in LMICs.

Alcohol use and immune reconstitution among HIV-infected patients on antiretroviral therapy in Nairobi, Kenya.

Studies on the effects of alcohol use on HIV disease progression have been contradictory, with at least one study finding a positive effect of low alcohol consumption on CD4 count. In addition, most such studies have taken place in the developed West. We investigated the association between alcohol use and immune reconstitution through CD4 count response among HIV-infected individuals on antiretroviral therapy (ART) at an urban sub-Saharan African clinic. This was a retrospective cohort study of treatment-naïve HIV-infected adults initiating ART in Nairobi, Kenya and followed for 12 months between January 2009 and December 2012. At enrollment, a standardized questionnaire was used to collect data on sociodemographic variables and alcohol consumption. CD4 count was measured every six months. Linear regression models assessed the association between CD4 count and alcohol consumption, categorized as abstinent, moderate, or hazardous. Overall, 854 participants were included, 522 of which were women, with 85 (25.6%) men and 50 (9.6%) women reporting any alcohol use, and 8 (2.4%) men and 7 (1.3%) women reporting hazardous drinking. At baseline, alcohol use was associated with higher education and socioeconomic status. Median CD4 count was higher among alcohol users compared to those who abstained at baseline and at 6 and 12 months post-ART initiation, although this was only significant at 6 months. There were no differences in adherence between abstainers and drinkers. While overall alcohol use was significantly associated with higher CD4 counts, moderate and hazardous use treated separately were not. We conclude that, while alcohol use was associated with higher CD4 counts at 12 months post-ART, the mechanism for this association is unclear but may reflect unmeasured socioeconomic or nutritional differences. Additional research is required on the specific drinking patterns of this population and the types of alcoholic beverages consumed to clarify this relationship.

Risk Factors for Hypoxia and Tachypnea Among Adolescents With Vertically-acquired HIV in Nairobi.

BACKGROUND: Chronic lung diseases are increasingly recognized complications of vertically-acquired HIV among adolescents in sub-Saharan Africa and may manifest with hypoxia or tachypnea. We sought to determine the prevalence of and risk factors for hypoxia and tachypnea among adolescents with vertically-acquired HIV in Nairobi, Kenya. METHODS: We performed a cross-sectional analysis of 258 adolescents with vertically-acquired HIV who were initiating care at the Coptic Hope Center for Infectious Diseases. Adolescents with documented pneumonia were excluded. Hypoxia was defined as resting oxygen saturation ≤92%, and tachypnea was based on the 99th percentile of age-appropriate respiratory rates. Logistic regression models adjusted for demographics, and HIV severity estimated odds ratios for risk of hypoxia and tachypnea associated with potential risk factors. RESULTS: Overall, 11% of adolescents had hypoxia and 55% had tachypnea. Advanced HIV [adjusted odds ratio (aOR): 2.41] and low CD4 (aOR: 1.74) were associated with greater hypoxia risk, but confidence intervals (CIs) were wide and included the null (95% CI: 0.93-6.23 and 0.69-4.39, respectively). Low CD4 (aOR: 2.45, 95% CI: 1.39-4.32), current antiretroviral therapy use (aOR: 0.48, 95% CI: 0.27-0.86) and stunted growth (aOR: 3.46, 95% CI: 1.94-6.18) were associated with altered tachypnea risk. CONCLUSIONS: Hypoxia and tachypnea are common among adolescents with vertically-acquired HIV. There was a suggestion that advanced HIV and low CD4 were associated with greater hypoxia risk. Low CD4, lack of antiretroviral therapy use and stunted growth are risk factors for tachypnea. Our findings highlight the chronic lung disease burden in this population and may inform diagnostic algorithms.

Psychological and social impacts of automated external defibrillators (AEDs) in the home.

BACKGROUND: The majority of cardiac arrests occur in the home. The placement of AEDs in the homes of at-risk patients may save lives through early defibrillation. However, the impact of having an AED in the home on psychological outcomes and quality-of-life is unknown. OBJECTIVE: The purpose of this research was to determine whether training in the use of and possessing an automated external defibrillator (AED) has an effect on a patient at risk's quality of life. METHODS: We investigated the psychological consequences of AED training and possession of such a device for patients who recently experienced an acute ischemic event. One hundred fifty eight patients and their family members were assigned at random to receive cardiopulmonary resuscitation (CPR) training (N=66) or AED/CPR training and possession of the device after training (N=92). We measured quality of life using the Short-Form (SF-36) survey and a 9-item survey we developed specifically for this study to measure differences in social activities and worries about being left alone. Participants answered these questions at enrollment, 2 weeks, 3 months, and 3 months after enrollment. RESULTS: Patients in the AED group reported lower (worse) scores on most SF-36 subscales at all periods, particularly in those subscales relating to social functioning. The differences were most often small and probably not clinically meaningful. The social activities/worry scales also favored the CPR group at all periods, but with no significant differences. CONCLUSIONS: Physicians counselling patients about AEDs should be aware of the potential effects the device may have on a patient's social functioning.

A community intervention by firefighters to increase 911 calls and aspirin use for chest pain.

OBJECTIVES: To test the effectiveness of an intervention, delivered face-to-face by local firefighters, designed to increase utilization of 911 and self-administration of aspirin for seniors experiencing chest pain. METHODS: King County, Washington was divided into 126 geographically distinct areas that were randomized to intervention and control areas. A mailing list identified households of seniors within these areas. More than 20,000 homes in the intervention areas were contacted by local firefighters. Data on all 911 calls for chest pain and self-administration of aspirin were collected from the medical incident report form (MIRF). The unit of analysis was the area. Firefighters delivered a heart attack survival kit (that included an aspirin) and counseled participants on the importance of aspirin and 911 use for chest pain. Main outcome measures were 911 calls for chest pain and aspirin ingestion for a chest pain event, obtained from the MIRFs that are collected by emergency medical services personnel for 2 years after the intervention. RESULTS: There were significantly more calls (16%) among seniors on the mailing list in the intervention than control areas in the first year after the intervention. Among the seniors who were not on the mailing list, there was little difference in the intervention and control areas. The results were somewhat sensitive to the analytical model used and to an outlier in the treatment group. CONCLUSIONS: A community-based firefighter intervention can be effective in increasing appropriate response to symptoms of a heart attack among elders.

Do older adults use the Internet for information on heart attacks? Results from a survey of seniors in King County, Washington.

BACKGROUND: Early treatment can reduce mortality from heart attacks. However, patient delay, especially among the elderly, has slowed progress in this area. One of the reasons for delay may be because of a lack of knowledge about symptoms of acute myocardial infarction (AMI) and treatment benefits. The Internet is a new and promising source of heart health information, but we know little about how elderly people use this medium. METHODS: This study investigates the demographic and psychosocial variables that are related to Internet access, health information seeking, and information seeking about heart attacks from the Internet among seniors. We interviewed seniors (N = 323) aged more than 65 years and asked them questions about Internet access, health information seeking, and information seeking on heart attacks, as well as demographic information, risk perceptions for AMI, and personal experience with AMI. RESULTS: The results showed that several demographic variables were related to access to the Internet. Only 7% of the seniors who reported access to the Internet had sought information on heart attacks from the Internet. Age, history of AMI, and family history of AMI were significant predictors of information seeking on heart attacks. This suggests that to date only a very small, high-risk group of seniors actually seeks information on heart attack emergencies from the Internet.

Evaluation of a public education program delivered by firefighters on early recognition of a heart attack.

The Heart Attack Survival Kit (HASK) project is a prospective, randomized trial, testing the effectiveness of an intervention delivered door-to-door by firefighters to increase use of 911 and ingestion of aspirin for symptoms of acute myocardial infarction (AMI) among seniors in King County, Washington. Firefighters visited 24,582 seniors in King County, Washington and delivered a Heart Attack Survival Kit. Another 24,191 senior households served as the control group. Outcomes of the program were measured by tracking 911 calls as well as survey data. This study reports on the results of the telephone survey with a random sample of seniors (N = 323) to assess their knowledge of and intentions to act during a heart emergency. Results of a logistic regression analysis showed that being female, being younger, and remembering the kit was significantly related to intentions to act appropriately to AMI symptoms. The results are discussed in terms of public education around AMI.

Out-of-hospital care of critical drug overdoses involving cardiac arrest.

OBJECTIVES: Death from acute drug poisoning, also termed drug overdose, is a substantial public health problem. Little is known regarding the role of emergency medical services (EMS) in critical drug poisonings. This study investigates the involvement and potential mortality benefit of EMS for critical drug poisonings, characterized by cardiovascular collapse requiring cardiopulmonary resuscitation (CPR). METHODS: The study population was composed of death events caused by acute drug poisoning, defined as poisoning deaths and deaths averted (persons successfully resuscitated from out-of-hospital cardiac arrest by EMS) in King County, Washington, during the year 2000. RESULTS: Eleven persons were successfully resuscitated and 234 persons died from cardiac arrest caused by acute drug poisoning, for a total of 245 cardiac events. The EMS responded to 79.6% (195/245), attempted resuscitation in 34.7% (85/245), and successfully resuscitated 4.5% (11/245) of all events. Among the 85 persons for whom EMS attempted resuscitation, opioids, cocaine, and alcohol were the predominant drugs involved, although over half involved multiple drug classes. Among the 11 persons successfully resuscitated, return of circulation was achieved in six following EMS cardiopulmonary resuscitation alone, in one following CPR and defibrillation, and in the remaining four after additional advanced life support. CONCLUSIONS: In this community, EMS was involved in the majority of acute drug poisonings characterized by cardiovascular collapse and may potentially lower total mortality by approximately 4.5%. The results show that, in some survivors, return of spontaneous circulation may be achieved with CPR alone, suggesting a different pathophysiology in drug poisoning compared with cardiac arrest due to heart disease.