Unintended Adverse Effects Research Articles

Three-Generation Reproductive Toxicity of Genetically Modified Maize with Cry1Ab and epsps Genes in Rats.

The genetically modified maize carrying an insect-resistant gene and herbicide-tolerant gene has substantial benefits for crop production. The three-generation reproductive toxicity of the maize was studied in this paper. One hundred and eighty Sprague-Dawley (SD) rats were divided into three groups, which were fed with a genetically modified maize (GM) diet, receptor maize (RM) diet, and AIN-93G (AIN) diet (used as control), respectively. The body weight, food consumption, reproductive parameters, hematological parameters, serum chemistry, organ weight, and histopathology for the three generations were examined, respectively. Minor differences were found between the GM group and the RM group or the AIN control group in terms of reproductive data, hematology, blood chemistry parameters, and organ index, but no macroscopic or histological adverse effects were found or considered as treatment-related. In conclusion, the three-generation study of genetically modified maize DBN9936 with Cry1Ab and epsps genes at a high level showed no unintended adverse effects on rats' reproductive system.

Tumor-Targeting Bacteria: As Vectors, Immunotherapeutic Agents And Tumor-Targeting Probes For Cancer Detection And Therapy

Cancer is the world's second leading cause of death in humans. Conventional anticancer therapies are often associated with lack of tumor specificity, failure to detect small metastases, increased resistance of tumors to anticancer drugs, and unintended adverse effects. Numerous alternative and better strategies in cancer treatment have been developed to overcome the negative effects of traditional cancer therapies. More than a century ago, William Coley, the father of cancer immounotherapy, laid the groundwork for bacterial anticancer therapy. Bacterial immunotherapy has been emerging as a potential anticancer therapy. Moreover, certain obligate and facultative anaerobic bacterial species are exploited as vectors for gene delivery to treat cancer. These genes encode for anticancer agents, cytokines, cytotoxic peptides, anti-angiogenic proteins, therapeutic molecules and prodrug-converting enzymes. Genetically engineered bacterial strains of Salmonella, Bifidobacterium, Clostridium and Listeria are widely used to deliver genes in anticancer therapy since they can selectively accumulate in solid tumors with a hypoxic/necrotic core in vivo, providing appealing delivery systems to target therapeutic agents and immunomodulatory molecules to the site of tumor. Certain genetically modified bacterial species such as Bifidobacterium longum and Bacillus licheniformis have been effectively used for the enzyme/prodrug therapy for cancer. Furthermore, certain anaerobic bacteria are emerging as potential tumor markers due to the increased mobility and the selectivity in germinating and multiplying in hypoxic/anoxic environments. Many of these novel developments have been studied extensively in different experimental models of cancer and certain clinical trials are ongoing for some treatment modalities. Although favourable results have shown so far, further studies and technological innovations are required to ensure the efficacy of bacterial anticancer therapy.

Intended or unintended adverse effects? The impact of ambiguous "Drink Responsibly" alcohol campaign messages on the drinking intentions of college students

Although alcohol companies promote “responsible drinking” health campaign messages voluntarily, critics are skeptical of the industry’s campaign, especially given that its messages are too ambiguous to be effective. This study examined how strategically ambiguous messages, in comparison to informative messages, impact college students’ perception of their knowledge as well as the psychological reactance tendency and subsequently influence the formation of attitudes and intent toward responsible drinking practices and alcohol consumption. How alcohol involvement level interacts with the type of message was also examined. An online experiment revealed that strategically ambiguous messages by alcohol companies may serve to solidify their consumer bases by promoting alcohol consumption among college students. When exposed to ambiguous messages, heavier drinkers reported their perceived knowledge level as significantly higher. The false or naïve perception of knowledge induced by ambiguous messages influenced college students’ formation of more positive attitudes toward drinking and consequently engendered greater intent to drink. While informative messages led to more psychological reactance – especially among heavier drinkers – such aroused reactance did not lead to more favorable attitudes toward drinking or intent to drink, meaning there was no boomerang effect of psychological reactance induced by informative messages. The study concludes that the industry’s alcohol responsibility message carries an “adverse effect” from a public health standpoint.

Do Start-Up Subsidies for the Unemployed Affect Participants' Well-Being? A Rigorous Look at (Un-)Intended Consequences of Labor Market Policies.

The literature on start-up subsidies (SUS) for the unemployed finds positive effects on objective outcome measures such as employment or income. However, little is known about effects on subjective well-being of participants. Knowledge about this is especially important because subsidizing the transition into self-employment may have unintended adverse effects on participants' well-being due to its risky nature and lower social security protection, especially in the long run. We study the long-term effects of SUS on subjective outcome indicators of well-being, as measured by the participants' satisfaction in different domains. This extends previous analyses of the current German SUS program ("Gründungszuschuss") that focused on objective outcomes-such as employment and income-and allows us to make a more complete judgment about the overall effects of SUS at the individual level. Having access to linked administrative-survey data providing us with rich information on pretreatment characteristics, we base our analysis on the conditional independence assumption and use propensity score matching to estimate causal effects within the potential outcomes framework. We perform several sensitivity analyses to inspect the robustness of our findings. We find long-term positive effects on job satisfaction but negative effects on individuals' satisfaction with their social security situation. Supplementary findings suggest that the negative effect on satisfaction with social security may be driven by negative effects on unemployment and retirement insurance coverage. Our heterogeneity analysis reveals substantial variation in effects across gender, age groups, and skill levels. Estimates are highly robust.

Effectively Communicating About HIV and Other Health Disparities: Findings From a Literature Review and Future Directions.

Despite significant progress in the prevention and treatment of HIV, disparities in rates of infection remain among key groups in the United States, including blacks and African Americans; Hispanics/Latinos; and men who have sex with men (MSM). The U.S. Department of Health and Human Services’ initiative, Ending the HIV Epidemic: A Plan for America, calls for addressing HIV-related disparities and reducing stigma and discrimination associated with HIV. The goal of this literature review was to identify approaches for effectively communicating about health disparities across the HIV care continuum. We reviewed the literature to investigate strategies used to communicate health disparities and to identify potential unintended adverse effects resulting from this messaging. Messages about health disparities often target subgroups at higher risk and can be framed in a variety of ways (e.g., social comparison, progress, impact, etiological). Studies have examined the effects of message framing on the risk perceptions, emotional reactions, and behaviors of individuals exposed to the messaging. The evidence points to several potential unintended adverse effects of using social comparison framing and individual responsibility framing to communicate about health disparities, and visual images and exemplars to target messages to higher-risk subgroups. There is not yet a clear evidence-based approach for communicating about health disparities and avoiding potential unintended effects. However, we offer recommendations for communicating about HIV-related disparities based on our findings. Because we found limited literature that addressed our research questions in the context of HIV, we propose a research agenda to build an evidence base for developing effective messages about HIV-related disparities.

Chronic toxicity study in Sprague-Dawley rats on transgenic rice T1c-19 with cry1C* gene

In the present study, a novel transgenic rice line T1c-19 carrying cry1C* gene was evaluated in Sprague-Dawley (SD) rats by a 52-week feeding study, aiming at determining its unintended effects. The rice T1c-19 and its parental rice were prepared at a level of up to 60.75% in the growth diet and 66.75% in the maintenance diet, respectively. AIN-93 diet was used as a nutritional control. All the diets were nutritionally balanced. Each group, with 48 rats of both genders, was fed the corresponding diet for 52 weeks. The results of clinical signs, body weight and food consumption of the transgenic rice group were comparable to those of the parental rice group. Clinical measurements were made on weeks 13, 26 and 52, and statistical significances were observed in several hematological and serum biochemical indices between the two rice groups and were not considered as treatment-related. The terminal histopathological examination showed some spontaneous lesions in all groups with no significant difference among them. Taken together, the results of the present 52-week chronic toxicity study of transgenic rice T1c-19 exerted no unintended adverse effects on SD rats.

Investigating the Roles of Donor Macrophages after Cardiac Transplantation

Heart transplantation is limited by donor availability, immune mediated rejection, and unintended adverse effects from immunosuppression. Expanding donor availability and immunologic compatibility are priorities. Donor-organ directed therapies have the potential to improve allograft survival while minimizing patient harm. The heart contains 2 ontogenically distinct tissue resident macrophage populations (CCR2- and CCR2+ macrophages) with divergent inflammatory and reparative functions. The exact role of donor macrophages after cardiac transplant remains unexplored. A better understanding of how donor intrinsic immunity influences allograft acceptance and survival may provide new opportunities to improve the outcomes of transplant recipients. We utilized a fully HLA-mismatched mouse heart transplant model in combination with two differing immunosuppression regimens: CTLA4-Ig (acute rejection model) and CTLA4 Ig + anti-CD40L Ab (graft tolerance model). We assessed donor macrophage composition, location, and dynamics at various time points following transplantation using genetic lineage tracing and imaging. The functional requirements for CCR2- and CCR2+ donor macrophages was assessed using transgenic mice that facilitate selective depletion of CCR2- or CCR2+ macrophages. We show that donor CCR2- and CCR2+ macrophages persist in the heart following transplantation. We demonstrate that donor CCR2- and CCR2+ macrophages display dynamic responses following IRI and rejection. Co-labelling with CD68 highlights the later composition of donor-derived CCR2+ macrophages, donor-derived CCR2- macrophages, and resident monocyte derived macrophages in the transplanted heart. Depletion of CCR2+ macrophages prior to transplantation resulted in prolonged allograft survival and reduced cardiomyocyte cell death. In contrast, deletion of CCR2- macrophages led to accelerated rejection, increased cardiomyocyte cell death, and exaggerated leukocyte infiltration. Donor-derived CCR2+ macrophages and donor-derived CCR2- macrophages persist in the cardiac transplant. Depletion of donor-derived CCR2+ macrophages led to graft rejection whereas removal of donor-derived CCR2- macrophages promoted graft survival. These data indicate that donor macrophages play key roles in acute cellular rejection after cardiac transplantation.

NUTRACEUTICALS AND HERBALS AS ADJUVANTS IN THE CHEMOTHERAPY OF CANCER? A REVIEW

Cancer is the third leading cause of death worldwide. The current cancer treatments such as chemotherapy and radiotherapy resulting in the development of unintended adverse effects that reduce the quality of life and economic burden in oncology patients. Nutraceuticals along with food value have natural bioactive components that have reassuring therapeutic properties in several diseases. Herbs of significant interest have been proven to prevent and treat various types of cancer and also reduce the side effects of chemotherapy and radiotherapy. The efficacy of nutraceuticals and herbs such as chemopreventive and chemotherapy is highlighted. We conclude that further studies are required to countersign the targeted approaches and efficacy of herbs and nutraceuticals in cancer patients as adjuvant therapy.

Lung protection in acute respiratory distress syndrome: what should we target?

Most clinical trials of lung-protective ventilation have tested one-size-fits-all strategies with mixed results. Data are lacking on how best to tailor mechanical ventilation to patient-specific risk of lung injury. Risk of ventilation-induced lung injury is determined by biological predisposition to biophysical lung injury and physical mechanical perturbations that concentrate stress and strain regionally within the lung. Recent investigations have identified molecular subphenotypes classified as hyperinflammatory and hypoinflammatory acute respiratory distress syndrome (ARDS), which may have dissimilar risk for ventilation-induced lung injury. Mechanically, gravity-dependent atelectasis has long been recognized to decrease total aerated lung volume available for tidal ventilation, a concept termed the 'ARDS baby lung'. Recent studies have demonstrated that the aerated baby lung also has nonuniform stress/strain distribution, with potentially injurious forces concentrated in zones of heterogeneity where aerated alveoli are adjacent to flooded or atelectatic alveoli. The preponderance of evidence also indicates that current standard-of-care tidal volume management is not universally protective in ARDS. When considering escalation of lung-protective interventions, potential benefits of the intervention should be weighed against tradeoffs of accompanying cointerventions required, for example, deeper sedation or neuromuscular blockade. A precision medicine approach to lung-protection would weigh. A precision medicine approach to lung-protective ventilation requires weighing four key factors in each patient: biological predisposition to biophysical lung injury, mechanical predisposition to biophysical injury accounting for spatial mechanical heterogeneity within the lung, anticipated benefits of escalating lung-protective interventions, and potential unintended adverse effects of mandatory cointerventions.

A comparison of integrated pest management and traditional practices for bagged maize stored in Nigeria

In grain markets in Nigeria, stored product insects can cause significant losses in quality and quantity of stored grains. Insect infestations in storehouses are usually controlled by the unilateral use of chemical insecticides, which have unintended adverse effects. In this study, approximately 15 MT of well-dried, Aflasafe™-treated maize was procured from a local farm settlement in January 2016. It was subsequently fumigated, mechanically cleaned and placed in 100-kg polypropylene bags for storage. The study was conducted during February–December 2016, to compare the effectiveness of traditional storage practice (TSP) with integrated pest management (IPM) practice. IPM for warehouse facilities focuses on adequate drying, inspection and cleaning of storehouses and their surroundings and regular examination of grain (IPMD). Traditional storage practice generally has little or no sanitation of the facility or regular examination of grain (monitoring) for insect pests. Study locations were markets in Ibadan, Oyo and Ilorin towns in Southwest and Northcentral Nigeria, respectively. Each market had two storehouses where TSP or IPMD was assigned; each storehouse had twenty-five bags of maize, which were sampled monthly to assess the effects of the two practices on stored maize insect populations and quality. Generally, from October to December, there tended to be more insects of all species in TSP than IPMD. Percent insect damaged kernels (%IDKNB) and weight loss (%WL) were also higher in TSP than IPMD during the October–December period. Percent germination in December was higher in IPMD (96.3%) than in TSP (85.3%). Aflatoxin levels in both TSP and IPMD did not exceed 1.9 ppb. Data from this study show that IPMD results in lower stored-product insect population levels and better maize quality than TSP. Thus, IPMD practice needs to be more widely adopted in storehouses in Nigeria and the rest of sub-Saharan Africa.

Correlations between opioid mortality increases related to illicit/synthetic opioids and reductions of medical opioid dispensing - exploratory analyses from Canada

BackgroundNorth America has been experiencing a persistent epidemic of opioid-related overdose mortality, which has increasingly been driven by fatalities from illicit, toxic opioids in most recent years. Patterns of synthetic opioid availability and related mortality are heterogeneous across Canada, and differing explanations exist as to their differentiated proliferation. We examined the perspective that heterogeneous province-based variations in prescription opioid availability, facilitated by various control strategies, post-2010 may have created regionally differential supply gaps for non-medical opioid use substituted by synthetic opioid products with differential impacts on mortality risks and outcomes in Canada.MethodsWe examined annual, prescription opioid dispensing rates and changes in the ten Canadian provinces (for the periods of 1) 2011–2018, 2) ‘peak-year’-to-2018) in Defined Daily Doses/1000 population/day, derived from data from a large representative, stratified sample of community pharmacies projected to a Canada total. Annual, provincial opioid-related mortality rates and changes for years 2016–2018 were calculated from federal data. We computed correlation values (Pearson’s R) between respective province-based change rates for prescription opioid dispensing and opioid-related mortality for the two over-time scenarios.ResultsAll but one province featured reductions in prescription opioid dispensing 2011–2018; seven of the ten provinces had increases in opioid mortality 2016–2018. The correlation between changes in opioid dispensing (2011–2018) and in opioid-mortality (2016–2018) was r = 0.63 (df = 8, p-value: 0.05); the correlation was r = 0.57 (df = 8, p-value: 0.09) for changes in opioid dispensing ‘peak year’-to-2018, respectively.ConclusionsQuasi-significant results indicate that recent increases in opioid-related deaths driven by illicit, synthetic opioids tended to be larger in provinces where reductions in prescription opioid availability have been more extensive. It is a plausible explanation that these reductions created supply gaps for non-medical opioid use increasingly filled by illicit, synthetic opioids differentially contributing to opioid-related deaths, generating un-intended adverse effects for previous interventions. General prevention measures to reduce opioid availability, and targeted prevention for at-risk opioid users exposed to toxic drug supply may be include counteractive effects and require coordinated reconciliation.

Role of donor macrophages after heart and lung transplantation.

Since the 1960s, heart and lung transplantation has remained the optimal therapy for patients with end-stage disease, extending and improving quality of life for thousands of individuals annually. Expanding donor organ availability and immunologic compatibility is a priority to help meet the clinical demand for organ transplant. While effective, current immunosuppression is imperfect as it lacks specificity and imposes unintended adverse effects such as opportunistic infections and malignancy that limit the health and longevity of transplant recipients. In this review, we focus on donor macrophages as a new target to achieve allograft tolerance. Donor organ-directed therapies have the potential to improve allograft survival while minimizing patient harm related to global suppression of recipient immune responses. Topics highlighted include the role of ontogenically distinct donor macrophage populations in ischemia-reperfusion injury and rejection, including their interaction with allograft-infiltrating recipient immune cells and potential therapeutic approaches. Ultimately, a better understanding of how donor intrinsic immunity influences allograft acceptance and survival will provide new opportunities to improve the outcomes of transplant recipients.

Corporate Law for Good People

This article offers a novel analysis of the field of corporate governance by viewing it through the lens of behavioral ethics. It calls for both shifting the focus of corporate governance to a new set of loci of potential corporate wrongdoing and adding new tools to the corporate governance arsenal. The behavioral ethics scholarship emphasizes the large share of wrongdoing generated by whose intention is to act ethically. Their wrongdoing stems from -- various cognitive and motivational processes that lead to biased decisions that seem legitimate. In the legal domain, corporate law provides the most fertile ground for the application of behavioral ethics since it encapsulates many of the features that the behavioral ethics literature found to confound the ethical judgment of good people, such as agency, group decisions, victim remoteness, vague directives and subtle conflict of interests. Bounded ethicality suggests a view of corporate law that is dramatically different than that portrayed by traditional legal and economic theorists. Not only does it suggest that wrongdoing can be committed by well-intentioned people who wish to do right, but also that the biases they display call for a radically different set of legal interventions than those advocated by standard economic theory. If standard theorizing views corporate agents as self-interest maximizers, bounded rationality perceives them as actors with varied and nuanced motivations that could benefit from subtle legal reforms. This Article's assessment of corporate governance through the behavioral ethical lens proceeds in three stages. First, it exposes potential wrongdoing by good people that conventional corporate governance does not address. Second, it suggests novel corporate governance interventions supported by behavioral ethics to address wrongdoing by good people. Third, it identifies existing interventions that according to behavioral ethics analysis may generate unintended adverse effects on the behavior of well-meaning corporate officers and exacerbate wrongdoing instead of mitigating it. As we will show bounded ethicality has important implications for a wide range of topics in corporate governance, such as board structure, independent directors, regulation of institutional investors and proxy advisory firms, the business judgment rule, and corporate and intra-board liability.

The Effects of International Scrutiny on Manufacturing Workers: Evidence from the Rana Plaza Collapse in Bangladesh

After the tragic factory collapse of Rana Plaza in 2013, both the direct reforms and indirect responses of retailers have plausibly affected workers in the Ready Made Garment (RMG) sector in Bangladesh. These responses included a minimum wage increase, high profile but voluntary audits, and an increased reluctance to subcontract to smaller factories. This paper uses six rounds of the Labor Force Survey and adopts a difference-in-difference approach to evaluate the net effects of these changes on garment workers, compared with workers in plausible control groups. Although employers have improved working conditions as intended by the reforms, the authors evidence adverse effects on several dimensions workers'outcomes in the years following Rana Plaza. While the reforms initially increased female workers'wages and the likelihood to hold a formal contract in the months that immediately followed Rana Plaza, they then declined in the following years. In contrast, no adverse effect is detected for male workers. The results suggest that regulations initially aimed at helping workers can have unintended adverse effects on some dimensions of workers'outcomes.

The Unintended Consequences of Ngo-Provided Aid on Government Services in Uganda

This paper studies the impact of the entry of a large foreign NGO which provides basic health services on the government’s capacity to provide similar services in rural Uganda. In villages with a government health worker at baseline, the NGO hires the government worker in half of the villages it enters. Where “poaching” occurs, overall healthcare and infant mortality worsen. In villages where the NGO hires a second worker who is not the government worker, health outcomes improve. In villages with no government health worker at baseline, NGO entry improves healthcare and health outcomes, but increases the closure of village schools, the other public good that relies on skilled labor, and reduces school attendance. Our results support the concern that NGOs can have unintended adverse effects on government services in contexts where skilled labor is scarce.

Immunotoxicity of Therapeutic Antibodies and Nanoparticles.

Therapeutic antibodies and nanotherapeutic drugs are of great concern due to their widespread use against numerous diseases worldwide. They are frequently used for targeted therapy under the assumption that they cause fewer side effects than nontargeted drugs. Despite their specificity and particular design for therapeutic actions, they might still exhibit unintended adverse effects in the immune system. Immunotoxicity reactions are mediated by immunomodulation, including immunostimulation and immunosuppression. The present review gives an overview on the adverse immunotoxic effects induced by therapeutic antibodies as well as nanotherapeutic drugs. In this context, future methods combining more efficient drug design with better tolerability and fewer adverse effects are discussed to ensure improved safety in the engineering of therapeutic antibodies and nanotherapeutics.

Design, synthesis and biological evaluation of a bi-specific vaccine against α-pyrrolidinovalerophenone (α-PVP) and 3,4-methylenedioxypyrovalerone (MDPV) in rats

α-PVP (α-pyrrolidinovalerophenone) and MDPV (3,4-methylenedioxypyrovalerone) are potent abused stimulants that are members of the synthetic cathinone class of drugs. Although these drugs are taken with recreational intent, high doses can lead to unintended adverse effects including agitation, cardiovascular effects, sympathomimetic syndromes, hallucinations, and psychoses. One possible treatment is the use of a vaccine to block or attenuate adverse medical effects. These studies report the preparation of a vaccine that generates high affinity antibodies specific for both drugs and the pharmacological testing of this vaccine in male rats. Alkylation of a hydroxy-α-PVP analog with an appropriate thiol-bearing linker afforded the hapten. When hapten-conjugated carrier protein was mixed with adjuvant, the resulting vaccine stimulated production of antibodies in male Sprague Dawley rats that were found to significantly reduce α-PVP- and MDPV-induced hyperlocomotion as well as to significantly reduce the concentrations of MDPV drugs in critical organs. The novel vaccine produced high affinity antibodies against MDPV, (R)-MDPV, (S)-MDPV, and α-PVP. Cross-reactivity testing against nine structurally similar cathinones showed very limited binding, and no binding to off-target endogenous and exogenous compounds. Antibodies generated by this bi-specific vaccine also significantly shortened the duration of locomotor activity induced by both drugs up to a dose of 5.6 mg/kg in male rats.

Military Coalitions and Crisis Duration

Forming a military coalition during an international crisis can improve a state’s chances of achieving its political goals. We argue that the involvement of a coalition, however, can have unintended adverse effects on crisis outcomes by complicating the bargaining process and extending the duration of crises. This argument suggests that crises involving coalitions should be significantly longer than crises without coalitions. However, other factors that affect crisis duration are also likely to influence coalition formation. Therefore, taking into account the endogeneity of the presence of a coalition is essential to testing our hypothesis. To deal with this inferential challenge, we develop a new statistical model that is an extension of instrumental variable estimation in survival analysis. Our analysis of 255 post–World War II interstate crises demonstrates that, even after accounting for the endogeneity of coalition formation, military coalitions tend to extend the duration of crises by approximately 284 days.

Parental Social Validity of the Mindfulness-Based OpenMind-Korea (OM-K) Preschool Program

There is a dearth of studies on the social validity of mindfulness-based school programs because the primary emphasis has been on effectiveness or efficacy of the programs in terms of academic engagement and performance, and classroom behavior of the students. The aim of the present study was to assess secondary outcomes of a mindfulness-based preschool program in terms of parental social validity. Forty parents whose children were in a larger study that evaluated the feasibility and acceptability of the OpenMind-Korea (OM-K) preschool program participated. At the end of the school year, these parents completed a 7-item social validity rating scale on the social significance of the OM-K program. The majority of the parents rated the OM-K program as being socially valid. They noted that their children learned skills that they could use both at home and in the preschool, and that they would recommend this program to other parents. The parents rated the program as simple to use, acceptable, effective, and without unintended adverse effects. Overall mean parent ratings of the social validity of the OM-K program were high and congruent with overall mean teacher feasibility and acceptability ratings.

Pharmacist Compliance With Therapeutic Guidelines on Diagnosis and Treatment Provision

Misuse and overselling of over-the-counter pharmaceuticals poses a major burden on both private and public health expenditures. To seek evidence on whether over-the-counter medication dispensing behavior complies or conflicts with the protocols indicated in practice standards and guidelines of a national professional pharmacy organization. This quality improvement study was undertaken in 205 pharmacies in the wider Brisbane, Australia, area. Two standardized patient (SP) scenarios were developed to evaluate noncompliant behavior. Data collection for scenario 1 was conducted between November 23 and December 9, 2016. Data collection for scenario 2 was conducted between September 1 and 28, 2017. A 2-sample test of proportions and a probit regression model were used to evaluate the likelihood of noncompliant treatments and overtreatments in each case scenario. Statistical analysis was performed from January 30 to June 21, 2018, and revised in May 2019. Outcomes were the observed likelihood of noncompliant treatments and overtreatments. Noncompliance is defined as treatments not complying with practice standards and guidelines set by the professional pharmacy society. Noncompliant treatments include undertreatment (patient did not receive necessary treatment) and overtreatments (patient was supplied with more than sufficient treatments) in both scenarios. In scenario 1, 9 trained female SPs visited 89 pharmacies to request emergency hormonal contraception from pharmacy staff. In 45 cases, SPs reported having unprotected intercourse within the last 24 hours (case 1A), and in 44 cases, SPs reported having unprotected intercourse more than 72 hours ago (case 1B), which is past the efficacy threshold of over-the-counter emergency hormonal contraception. In scenario 2, 11 SPs (5 male and 6 female) visited 150 pharmacies (154 visits in total) to request treatment for family members or a partner with symptoms indicating bacterial conjunctivitis (case 2A; n = 73) or viral conjunctivitis (case 2B; n = 81). In scenario 1-dispensing emergency hormonal contraception when physician referral is recommended-21 of 44 pharmacists (47.7%) in case 1B violated the recommendation by selling the over-the-counter medication. With the inclusion of both no physician referral and emergency hormonal contraception sold, this rate increased to 79.5% (35 of 44 pharmacists). In scenario 2-1 case each of bacterial and viral conjunctivitis-overtreatment occurred in 55 of 154 cases (35.7%). In both scenarios, 140 of 243 pharmacies (57.6%) followed dispensing behavior compliant with the protocol, while 76 of 243 pharmacies (31.3%) involved some form of overtreatment or overselling of medication. Some evidence of an association between sex of SP and pharmacist was also found. Although the market for dispensing over-the-counter medication in Australia is regulated, relatively high rates of overtreatment and some cases of undertreatment were observed in this study. Given the unintended adverse effects, including overuse of antibiotics and corticosteroids, these observations suggest the advisability of regulatory intervention ensuring compliance with professional protocols.