Assessment of BMI and Venous Thromboembolism Rates in Patients on Standard Chemoprophylaxis Regimens After Undergoing Free Tissue Transfer to the Head and Neck.

Importance: Venous thromboembolism (VTE) is a severe complication after free tissue transfer to the head and neck (H&N). Enoxaparin 30 mg twice daily (BID) is a common regimen for chemoprophylaxis. However, differences in enoxaparin metabolism based on body weight may influence its efficacy and safety profile. Objective: To assess the association between BMI and postoperative VTE and hematoma rates in patients treated with prophylactic enoxaparin 30 mg BID. Design, Setting, and Participants: This was a retrospective review of a prospectively collected cohort from 2012 to 2022. Postoperative VTE, hematoma, and free flap pedicle thrombosis were recorded within 30 days of index surgery. The setting was a tertiary academic referral center. Participants included patients undergoing H&N reconstruction with free flaps that received fixed-dose subcutaneous enoxaparin 30 mg BID postoperatively. Statistical analysis was conducted from April to May 2022. Main Outcomes and Measures: Outcomes include incidence of VTE, hematoma, and flap pedicle thrombosis events within 30 days of the surgery. Univariate and multivariable regression models were used to evaluate associations between BMI and other patient factors with these outcomes. Results: Among the 765 patients included, 262 (34.24%) were female; mean (SD) age was 60.85 (12.64) years; and mean (SD) BMI was 26.36 (6.29). The rates of VTE and hematoma in the cohort were 3.92% (30 patients) and 5.09% (39 patients), respectively. After adjusting for patient factors, BMI was the only factor associated with VTE (OR, 1.07; 95% CI, 1.015-1.129). Obesity (BMI >30) was associated with increased odds of VTE (OR, 2.782; 95% CI, 1.197-6.564). Hematoma was not associated with BMI (OR, 0.988; 95% CI, 0.937-1.041). Caprini score of at least 9 was not associated with VTE (OR, 1.259; 95% CI, 0.428-3.701). Conclusions and Relevance: This cohort study found that obesity was associated with an increased risk of VTE in patients after microvascular H&N reconstruction and while on standard postoperative chemoprophylaxis regimens. This association may suggest insufficient VTE prophylaxis in this group and a potential indication for weight-based dosing.

Cost-Effective Modeling of Thromboembolic Chemoprophylaxis for Total Ankle Arthroplasty.

BACKGROUND: Symptomatic venous thromboembolism (VTE) following total ankle arthroplasty (TAA) can cause substantial morbidity and mortality. To prevent this complication, surgeons often prescribe postoperative chemoprophylaxis. However, much controversy exists regarding the efficacy of chemoprophylaxis because of the limited studies exploring its use. Furthermore, even less is known about its cost-effectiveness. Therefore, this study sought to determine the cost-effectiveness of commonly prescribed chemoprophylactic agents using a break-even analysis economic model. METHODS: The literature was searched, and an online database was used to identify patients who developed a symptomatic VTE after undergoing TAA. Our institutional records were used to estimate the cost of treating a symptomatic VTE, and an online drug database was used to obtain the cost of commonly prescribed chemoprophylactic agents. A break-even analysis was then performed to determine the final break-even rate necessary to make a drug cost-effective. RESULTS: The low and high rates of symptomatic VTE were determined to be 0.46% and 9.8%. From 2011 to 2021, a total of 3455 patients underwent total ankle arthroplasty. Of these patients, 16 developed a postoperative symptomatic VTE (1.01%). Aspirin 81 mg was cost-effective if the initial symptomatic VTE rates decreased by an absolute risk reduction (ARR) of 0.0003% (NNT = 31 357). Aspirin 325 mg was also cost-effective if the initial rates decreased by an ARR 0.02% (NNT = 5807). Likewise, warfarin (5 mg) was cost-effective at all initial rates with an ARR of 0.02% (NNT = 4480). In contrast, enoxaparin (40 mg) and rivaroxaban (20 mg) were only cost-effective at higher initial symptomatic VTE rates with ARRs of 1.48% (NNT = 68) and 5.36% (NNT = 19). Additional analyses demonstrated that enoxaparin (40 mg) and rivaroxaban (20 mg) become cost-effective when costs of treating a symptomatic VTE are higher than our estimates. CONCLUSION: Chemoprophylaxis following TAA can be cost-effective. A tailored approach to VTE prophylaxis with cost-effectiveness in mind may be beneficial to the patient and health system.

Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. METHODS: For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine-pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. FINDINGS: 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0-78·8), and 54·5% children (95% CI 50·4-58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2-77·3] treated per month and 53·0% [48·5-57·4] treated four times). In 779 individual case safety reports over 2015-16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7-93·4) over 28 days in case-control studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015-16, the estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular markers of resistance occurred at low frequencies. In individuals aged 10-30 years without SMC, the combined mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and 184Tyr]) had a prevalence of 0·7% (95% CI 0·4-1·2) in 2016 and 0·4% (0·1-0·8) in 2018 (prevalence ratio 0·5 [95% CI 0·2-1·2]), and the quintuple mutation associated with resistance to sulfadoxine-pyrimethamine (triple mutation in pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1-0·5) in 2016 and 1·0% (0·6-1·6) in 2018 (prevalence ratio 4·8 [1·7-13·7]). The weighted average economic cost of administering four monthly SMC treatments was US$3·63 per child. INTERPRETATION: SMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via door-to-door campaigns. Markers of resistance to sulfadoxine-pyrimethamine and amodiaquine remained uncommon, but with some selection for resistance to sulfadoxine-pyrimethamine, and the situation needs to be carefully monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central Africa. FUNDING: Unitaid.

Questions and Answers on Practical Thrombotic Issues in SARS-CoV-2 Infection: A Guidance Document from the Italian Working Group on Atherosclerosis, Thrombosis and Vascular Biology.

In patients with coronavirus disease 2019 (COVID-19), the prevalence of pre-existing cardiovascular diseases is elevated. Moreover, various features, also including pro-thrombotic status, further predispose these patients to increased risk of ischemic cardiovascular events. Thus, the identification of optimal antithrombotic strategies in terms of the risk-benefit ratio and outcome improvement in this setting is crucial. However, debated issues on antithrombotic therapies in patients with COVID-19 are multiple and relevant. In this article, we provide ten questions and answers on risk stratification and antiplatelet/anticoagulant treatments in patients at risk of/with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on the scientific evidence gathered during the pandemic.

Effectiveness and safety of the pre-prescription of garenoxacin in comparison to moxifloxacin for low-risk febrile neutropenia in breast cancer patients undergoing adjuvant and neoadjuvant chemotherapy.

PURPOSE: The purpose of this study was to compare the efficacy of the pre-prescription of garenoxacin mesylate hydrate (GRNX) with that of moxifloxacin hydrochloride (MFLX) in the management of breast cancer patients with low-risk febrile neutropenia. METHODS: Data from female patients who had been instructed to take previously prescribed oral GRNX or MFLX for 3 days during adjuvant and neoadjuvant chemotherapy if their body temperature exceeded 38 °C were analyzed. This study compared the effectiveness between these fluoroquinolones using a propensity score matching analysis. RESULTS: The 330 patients received 1192 administrations of chemotherapy between May 2007 and April 2014 and 136 (41.2%) patients had a total of 212 (17.8%) febrile episodes. The frequencies of febrile episodes were 19.5% (113/579) and 16.2% (99/613) in the GRNX and MFLX groups, respectively. After propensity score matching, 384 episodes were matched in each group. Febrile events occurred in 80 and 56 cases in the GRNX and MFLX groups, respectively. Treatment success was identified in 80.0% (64/80) of cases in the GRNX group and 64.3% (36/56) of cases in the MFLX group (P = 0.0494). Additionally, the therapeutic use of granulocyte-colony stimulating factor was 6.3% (5/80) of cases in the GRNX group and 17.9% (10/56) of cases in the MFLX group (P = 0.0498). There were few differences in the frequency of adverse effects between the two groups. CONCLUSIONS: These results indicate that the pre-prescription of GRNX may be a more effective option for the management of low-risk febrile neutropenia during adjuvant and neoadjuvant chemotherapy for breast cancer.

Use of prophylactic growth factors and antimicrobials in elderly patients with cancer: a review of the Medicare database.

PURPOSE: Growth factors and antimicrobials can reduce complications of chemotherapy-induced myelosuppression. Their prophylactic use in elderly patients is important given the associated comorbidity in this age group. There is a developing trend by payers to include supportive care agents in chemotherapy care bundles, which could affect clinical practice. We examined whether the febrile neutropenia (FN) risk categories can be used to describe utilization in the Centers for Medicare & Medicaid fee-for-service system in older adults. METHODS: We conducted a retrospective cohort study using the Medicare 20% sample data to describe growth factor and antimicrobial use patterns in patients receiving chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL). RESULTS: The highest percentage of patients receiving granulocyte colony-stimulating factor (GCSF) within the first 5 days of a chemotherapy cycle were on high-FN-risk regimens, particularly for cycle 1 (73.7%, breast cancer; 61.5%, NHL) and cycle 2 (75.9%, breast cancer; 77.5%, NHL). Chemotherapy regimens for lung cancer are less myelotoxic, and growth factor use was more likely with latter cycles. Antibiotic use was lower at 15% within a cycle and appeared to be in response to complications. CONCLUSION: Practitioners use GCSF and antibiotics for elderly patients treated with potentially toxic chemotherapy, while comorbidity burden plays a role for patients treated with less myelotoxic regimens. The complexity of these choices in clinical practice should be considered in the proposed reimbursement changes being piloted by Medicare and private insurance companies seeking treatment cost reductions, as altered use could affect safety and efficacy.

Chemoprevention of colorectal neoplasia.

BACKGROUND: Colorectal cancer is a common and often fatal malignancy. Currently, the modifications that alter disease outcome include early symptom recognition, population screening as well as improved surgical and adjuvant treatments. Preventative strategies have been limited with little evidence that lifestyle changes significantly alter risk. There is however a growing awareness of a potential role for chemoprevention in some patient groups. This study aimed to review the literature associated with chemoprevention in colorectal cancer. METHODS: An electronic literature search of MEDLINE and Embase databases was performed on PubMed for studies detailing the use of chemoprevention agents in colon and rectal cancer. The search was limited to clinical trials on adult humans (>16 years of age) published in English since 1990. RESULTS: The strongest evidence is for non-steroidal anti-inflammatory drugs slowing polyp progression, notably Sulindac and aspirin in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, respectively. There is also increasing evidence that continuing use of low-dose aspirin reduces long-term incidence of colorectal cancers. Cyclooxygenase 2 inhibitors also have a potential role but cardiac toxicity currently limits their use. Folic acid, statins, antioxidants, calcium and 5-aminosalicylic acid lack evidence to support their use at present. CONCLUSIONS: Currently, there is not enough evidence to support the implementation of a chemopreventative agent for general use. However, there appears to be a role for aspirin in selected subgroups.

Historical Review: Problematic Malaria Prophylaxis with Quinine.

Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century. Compliance was difficult to enforce even in organized groups such as the military, and its prophylaxis potential was often questioned. Severe adverse events such as blackwater fever occurred rarely, but its relationship to quinine remains uncertain. Quinine prophylaxis was often counterproductive from a public health viewpoint as it left large numbers of persons with suppressed infections producing gametocytes infective for mosquitoes. Quinine was supplied by the first global pharmaceutical cartel which discouraged competition resulting in a near monopoly of cinchona plantations on the island of Java which were closed to Allied use when the Japanese Imperial Army captured Indonesia in 1942. The problems with quinine as a chemoprophylactic drug illustrate the difficulties with medications used for prevention and the acute need for improved compounds.

Aerosolised liposomal amphotericin B to prevent aspergillosis in acute myeloid leukaemia: Efficacy and cost effectiveness in real-life.

Chemotherapy-induced neutropenia can be complicated by invasive pulmonary aspergillosis (IPA). In 2008, liposomal amphotericin B (L-AmB) inhalation was shown to prevent IPA in a placebo-controlled trial. Patients with acute myeloid leukaemia (AML) are the subset of haematology patients at high risk for IPA. In 2008, L-AmB inhalation prophylaxis became the standard of care for all AML patients in Erasmus MC. In this study, the efficacy and cost effectiveness of L-AmB inhalation were evaluated in a prospective cohort of AML patients. In total, 127 consecutive AML patients received chemotherapy and prophylactically inhaled L-AmB during their first and second chemotherapy cycles; 108 patients treated for AML at the same sites from 2005-2008 served as controls. A standardised diagnostic protocol was used and probable/proven IPA served as the primary endpoint. Diagnostic and therapeutic costs were also comprehensively analysed and compared. A significant decrease in probable/proven IPA in the L-AmB inhalation group was observed (L-AmB 9.5% vs. controls 23.4%; P=0.0064). Systemic antifungal therapy given at any time during the entire AML therapy decreased from 52.8% to 29.9%. Per-patient equipment and drug costs for L-AmB inhalation (1292 €/patient) were more than compensated for by a decrease in costs for diagnostics and therapeutic voriconazole use (-1816 €/patient). No serious adverse events related to L-AmB inhalation were observed. In an unselected AML patient group, L-AmB inhalation resulted in a significant and substantial decrease in IPA and was cost saving. Now that azole resistance is more frequent, non-azole-based prophylaxis may become an attractive strategy.

Cancer Among Children With Perinatal Exposure to HIV and Antiretroviral Medications--New Jersey, 1995-2010.

BACKGROUND: Concerns remain regarding the cancer risk associated with perinatal antiretroviral (ARV) exposure among infants. No excessive cancer risk has been found in short-term studies. METHODS: Children born to HIV-infected women (HIV-exposed) in New Jersey from 1995 to 2008 were identified through the Enhanced HIV/AIDS Reporting System and cross-referenced with data from the New Jersey State Cancer Registry to identify new cases of cancer among children who were perinatally exposed to ARV. Matching of individuals in the Enhanced HIV/AIDS Reporting System to the New Jersey State Cancer Registry was conducted based on name, birth date, Social Security number, residential address, and sex using AutoMatch. Age- and sex-standardized incidence ratio (SIR) and exact 95% confidence intervals (CIs) were calculated using New Jersey (1979-2005) and US (1999-2009) cancer rates. RESULTS: Among 3087 children (29,099 person-years; median follow-up: 9.8 years), 4 were diagnosed with cancer. Cancer incidence among HIV-exposed children who were not exposed to ARV prophylaxis (22.5 per 100,000 person-years) did not differ significantly from the incidence among children who were exposed to any perinatal ARV prophylaxis (14.3 per 100,000 person-years). Furthermore, the number of cases observed among individuals exposed to ARV did not differ significantly from cases expected based on state (SIR = 1.21; 95% CI: 0.25 to 3.54) and national (SIR = 1.27; 95% CI: 0.26 to 3.70) reference rates. CONCLUSIONS: Our findings are reassuring that current use of ARV for perinatal HIV prophylaxis does not increase cancer risk. We found no evidence to alter the current federal guidelines of 2014 that recommend ARV prophylaxis of HIV-exposed infants.

Model-based cost-effectiveness analyses for prostate cancer chemoprevention : a review and summary of challenges.

BACKGROUND AND PURPOSE: Decision-analytic modelling is often used to examine the economics associated with using a specific treatment. As a result, it is important to understand structural and methodological approaches used in published decision-analytic models for examining the cost effectiveness of 5α-reductase inhibitors (5ARIs) for prostate cancer (PCa) chemoprevention. This understanding allows us to provide recommendations for using decision modelling in future economic evaluations of chemoprevention for PCa. METHODS: A review of the published literature was performed using MEDLINE and the Cochrane Library to identify studies involving mathematical decision models that evaluated 5ARIs for PCa chemoprevention. Published articles were reviewed and key modelling components were extracted and summarized. Recommendations for developing future decision models to examine the economic consequences of PCa chemoprevention were presented. RESULTS: We identified seven published models of PCa chemoprevention. All the models identified used a Markov framework with time horizons ranging from 4 years to lifetime. Due to the wide range of patient risk groups examined, PCa risk data were taken from the Surveillance, Epidemiology, and End Results (SEER) and other databases or estimates published in relevant clinical trials. Treatment effects included change in the incidence of high- and low-grade PCa and impacts on benign prostate hyperplasia. Adverse events were considered to affect compliance, discontinuation and quality of life. Quality-of-life impacts were similar among studies. Examination of modelling parameter sensitivities was comprehensive. CONCLUSIONS: Published models have examined the cost effectiveness of PCa chemoprevention; however, limitations exist. Decision models should take into account the full PCa clinical pathway when compiling health states. The time horizon should be long enough to consider the full benefit of chemoprevention while allowing actual time receiving the drug to occur from the start of the model until a man's life expectancy is less than 10 years. Baseline PCa risk should be specific to the population of concern. Models should examine the impact on both low- and high-grade tumours and account for the impact of 5ARIs on benign prostatic hyperplasia. Because chemoprevention has an upfront effect, the structure of the model should be constructed so that the downstream effect of avoiding or delaying recurrence can be considered. Adverse events due to chemoprevention should be considered through compliance, discontinuation or quality-of-life impact, and understanding the impact of avoiding PCa and benign prostatic hyperplasia events are important model properties.

Chemoprophylaxis in malaria: drugs, evidence of efficacy and costs.

This review concentrates on different aspects of malaria chemoprophylaxis, namely drug combinations, resistance, impact of malaria prevention in pregnancy and cost effectiveness. A MEDLINE search was performed for all articles with the key word 'Malaria' in the title field and 'Prophylaxis' in any field. The search was restricted to articles published in English within the last decade (1999-2009). Data sources included review articles published in core clinical journals, cohort studies, interventional studies, case control studies and cross sectional analyses. The mechanism of action, trial evidence of efficacy, side effects and geographical distribution of resistance is discussed for each prophylactic drug regimen. Impact of prophylaxis in pregnancy and the cost considerations are discussed under two separate sub topics.

[Postoperative nausea and vomiting and opioid-induced nausea and vomiting: guidelines for prevention and treatment]. / Recomendaciones de prevención y tratamiento de las náuseas y vómitos postoperatorios y/o asociados a las infusiones de opioides.

Postoperative nausea and vomiting (PONV) causes patient discomfort, lowers patient satisfaction, and increases care requirements. Opioid-induced nausea and vomiting (OINV) may also occur if opioids are used to treat postoperative pain. These guidelines aim to provide recommendations for the prevention and treatment of both problems. A working group was established in accordance with the charter of the Sociedad Española de Anestesiología y Reanimación. The group undertook the critical appraisal of articles relevant to the management of PONV and OINV in adults and children early and late in the perioperative period. Discussions led to recommendations, summarized as follows: 1) Risk for PONV should be assessed in all patients undergoing surgery; 2 easy-to-use scales are useful for risk assessment: the Apfel scale for adults and the Eberhart scale for children. 2) Measures to reduce baseline risk should be used for adults at moderate or high risk and all children. 3) Pharmacologic prophylaxis with 1 drug is useful for patients at low risk (Apfel or Eberhart 1) who are to receive general anesthesia; patients with higher levels of risk should receive prophylaxis with 2 or more drugs and baseline risk should be reduced (multimodal approach). 4) Dexamethasone, droperidol, and ondansetron (or other setrons) have similar levels of efficacy; drug choice should be made based on individual patient factors. 5) The drug prescribed for treating PONV should preferably be different from the one used for prophylaxis; ondansetron is the most effective drug for treating PONV. 6) Risk for PONV should be assessed before discharge after outpatient surgery or on the ward for hospitalized patients; there is no evidence that late preventive strategies are effective. 7) The drug of choice for preventing OINV is droperidol.

Determining utility values related to malaria and malaria chemoprophylaxis.

BACKGROUND: Chemoprophylaxis for travellers' malaria is problematic. Decision modeling may help determine optimal prevention strategies for travellers' malaria. Such models can fully assess effect of drug use and disease on quality of life, and help travellers make informed values based decisions. Such models require utility values reflecting societal preferences over different health states of relevance. To date, there are no published utility values relating to clinical malaria or chemoprophylaxis adverse events. METHODS: Utility estimates for health states related to falciparum malaria, sequelae and drug-related adverse events were obtained using a self-administered visual analogue scale in 20 individuals. Utility values for health states related to clinical malaria were obtained from a survey of 11 malaria experts questioned about length of hospital stay or equivalent disability with simple and severe travellers' malaria. RESULTS: The general public (potential travellers), were more tolerant of taking prophylaxis if associated with no or mild AEs and least tolerant of mild sequelae from malaria and severe drug related events. The rating value reported for taking no prophylaxis was quite variable. Tropical medicine specialists estimated a mean hospital stay 3.23 days (range 0.5-4.5 days) for simple and 6.36 days (range 4.5-7 days) for severe malaria. CONCLUSIONS: This study provides a benchmark for important utility value estimates for modeling malaria and drug-related outcomes in non-immune travellers.

Assessment of adverse events associated with antiretroviral regimens for postexposure prophylaxis for occupational and nonoccupational exposures to prevent transmission of human immunodeficiency virus.

OBJECTIVE: To assess adverse events associated with antiretroviral regimens for human immunodeficiency virus (HIV) postexposure prophylaxis (PEP), with a particular focus on the treatment combination of zidovudine, lamivudine, and tenofovir (ZDV-3TC-TDF). METHODS: Retrospective chart review for individuals who received HIV PEP for occupational and nonoccupational exposure, and multivariate analyses to identify risk factors for noncompletion of PEP and adverse events associated with PEP. SETTING: University of Rochester Health Service Occupational Health Program and University of Rochester AIDS Center. PARTICIPANTS: Healthcare workers who received HIV PEP for occupational exposure from January 1, 1999, to December 31, 2004, and individuals who received HIV PEP for nonoccupational exposure from January 1, 2002, to December 31, 2004.Results. We found increased rates of nausea among subjects who received treatment with ZDV-3TC-TDF and subjects who received treatment with zidovudine, lamivudine, and indinavir (ZDV-3TC-IDV). Analyses showed that female sex was a risk factor for nausea. Compared with subjects who received treatment with ZDV-3TC-TDF, subjects who received treatment with ZDV-3TC-IDV were less likely to not complete the HIV PEP for occupational exposure. CONCLUSION: Preventive treatment of adverse events may be necessary to ensure completion of HIV PEP.

Anticipating demand for emergency health services due to medication-related adverse events after rapid mass prophylaxis campaigns.

OBJECTIVES: Mass prophylaxis against infectious disease outbreaks carries the risk of medication-related adverse events (MRAEs). The authors sought to define the relationship between the rapidity of mass prophylaxis dispensing and the subsequent demand for emergency health services due to predictable MRAEs. METHODS: The authors created a spreadsheet-based computer model that calculates scenario-specific predicted daily MRAE rates from user inputs by applying a probability distribution to the reported timing of MRAEs. A hypothetical two- to ten-day prophylaxis campaign for one million people using recent data from both smallpox vaccination and anthrax chemoprophylaxis campaigns was modeled. RESULTS: The length of a mass prophylaxis campaign plays an important role in determining the subsequent intensity in emergency services utilization due to real or suspected adverse events. A two-day smallpox vaccination scenario would produce an estimated 32,000 medical encounters and 1,960 hospitalizations, peaking at 5,246 health care encounters six days after the start of the campaign; in contrast, a ten-day campaign would lead to 41% lower peak surge, with a maximum of 3,106 encounters on the busiest day, ten days after initiation of the campaign. MRAEs with longer lead times, such as those associated with anthrax chemoprophylaxis, exhibit less variability based on campaign length (e.g., 124 out of an estimated 1,400 hospitalizations on day 20 after a two-day campaign versus 103 on day 24 after a ten-day campaign). CONCLUSIONS: The duration of a mass prophylaxis campaign may have a substantial impact on the timing and peak number of clinically significant MRAEs, with very short campaigns overwhelming existing emergency department (ED) capacity to treat real or suspected medication-related injuries. While better reporting of both incidence and timing of MRAEs in future prophylaxis campaigns should improve the application of this model to community-based emergency preparedness planning, these results highlight the need for coordination between public health and emergency medicine planning for infectious disease outbreaks to avoid preventable surges in ED utilization.