The patient developed bigeminy while in the ED but remained hemodynamically stable and did not have a change in her mental status. Her electrolytes were replaced with oral and intravenous potassium, with improvement of her arrythmia and symptoms. She declined central line placement for more rapid replacement.Random urine electrolytes were obtained after the patient was admitted to the PICU . Nephrology was consulted because these results demonstrated an elevated urine anion gap suggestive of RTA. The patient’s symptoms completely resolved once her electrolytes were repleted. She was found to have positive antinuclear and anti–Sjögren’s-syndrome-related antigen A autoantibodies, leading to the diagnosis of Sjögren’s syndrome, despite a lack of phenotypic features. The patient’s urine anion gap was indeterminate for the etiology of her non-anion gap metabolic acidosis; however, her urine osmolar gap of less than 150 milliosmoles per kilogram suggested type 1 or type 4 RTA as the etiology. This coupled with laboratory findings suggestive of autoimmune disease led to the diagnosis of type 1 RTA. Her RTA was treated with potassium supplementation and alkali therapy to achieve a normal serum bicarbonate concentration. Unfortunately, the patient has not been compliant with her home therapy and has required multiple hospitalizations since her original presentation. Her presentation and urine anion gap strongly suggest toluene toxicity, but the patient repeatedly denied insufflating glue and there is no diagnostic test for toluene.Hyperchloremic,hydroponic stands hypokalemic metabolic acidosis is a condition all emergency providers should be prepared to diagnose and manage.

In this case, the patient presented with a cardiac arrhythmia due to severe hypokalemia. The underlying etiology of the hypokalemia should be sought while simultaneously treating the condition. The initial ED evaluation includes obtaining a basic metabolic panel and a urinalysis. Once it is determined that the patient does not have a serum anion gap, the clinician should consider three broad categories of non-anion gap acidosis and their etiologies: increased acid production; loss of bicarbonate; and decreased renal excretion of acid .Type 1 or distal RTA is a primary problem of urine acidification due to impaired hydrogen ion secretion in the distal convoluted tubules. The underlying etiology in adults is usually autoimmune diseases such as Sjögren’s syndrome or rheumatoid arthritis.In pediatrics, the cause is usually a hereditary gene mutation for either the basolateral chloridebicarbonate exchanger or the apical hydrogenadenosine triphosphatase gene.Lastly, a distal RTA can be iatrogenic due to ifosfamide, a chemotherapeutic analog of cyclophosphamide.Type 2 or proximal RTA is a primary problem of impaired bicarbonate reabsorption leading to increased bicarbonate loss.In adults, the underlying etiology is most commonly proximal tubular toxicity from increased exertion of monoclonal immunoglobulin light chains as seen in multiple myeloma.Type 2 RTAs are seen in Fanconi syndrome , and in patients prescribed carbonic anhydrase inhibitors .In pediatric patients, type 2 RTAs are usually idiopathic, but they can be due to a complication from chemotherapy, cystinosis , or inherited mutations in the KCNJ15 and SLC4A4 genes.The term “type 3 RTA” is rarely used as it is now considered a combination of types 1 and 2. Type 4 RTA is beyond the scope of this discussion. The test of choice when evaluating for a RTA is urine electrolytes so that the clinician can calculate how much ammonium is being excreted.18One of the most populated countries in the Middle East and North Africa region is Iran where over one million people are estimated to use illicit drugs. Moreover, the number of people who inject drugs is estimated to be 280 per 100,000 population, about half of whom are infected with hepatitis C virus and around 13.8% are living with human immunodeficiency virus.

To reduce HIV, HCV, and other blood borne infections among PWID, a comprehensive and innovative harm reduction program has been implemented in Iran. Currently, healthcare facilities including voluntary counseling and testing centers, HR centers for vulnerable women, shelters, prisons, antenatal clinics, and drop-in centers provide onsite or outreach HR services to PWID. These services include but are not limited to opioid agonist therapy by methadone, buprenorphine, or opium tincture, as well as needle and syringe programs , VCT, and free condom distribution. Although buprenorphine maintenance therapy and opium tincture are available in Iran, methadone maintenance treatment programs are more common. MMT programs were initially implemented in pilot projects in 2002; however, they were significantly scaled up in public and private clinical settings from 2003-2007. By September 2014, MMT was offered to PWID at 5744 private centers and 239 public centers supervised by State Welfare Organization, medical sciences universities, or prisons’ organization. As of 2018, over 700,000 participants have received MMT programs in these centers. The cost of MMT services is considerably lower in public centers. OAT in PWID has been associated with several beneficial public health outcomes including decreasing the rate of fatal and non-fatal overdose, reducing the rate of HIV and HCV transmission, lowering the rate of violence, diminishing social costs associated with drug use, increasing PWID’s quality of life, and improving their employment status. For PWID who are less connected to healthcare services, OAT could also represent a gateway to other services such as primary health care, HIV testing and counseling, antiretroviral therapy, and tuberculosis, HCV, and sexually transmitted infections care. Our understanding of the prevalence and patterns of OAT uptake among PWID in Iran is limited. To monitor the impact of OAT programs in prevention of HIV, HCV, and hepatitis B virus , it is crucial to know the current level of OAT uptake among PWID in Iran. In response, we aimed to identify the prevalence and trend of OAT among PWID and determine the factors associated with OAT uptake using the data collected in two national consecutive bio-behavioral surveillance surveys conducted in urban settings across Iran in 2010 and 2014.

Data from the 2010 and 2014 HIV national bio-behavioral surveillance surveys were used to assess the prevalence of OAT uptake among PWID in Iran. As PWID bear the highest burden of HIV on Iran, nation-wide surveys are conducted every few years to help monitor the trend of HIV and its related risk behaviors among this population and inform the national HIV response. The 2010 and 2014 surveys were conducted in 10 geographically diverse cities. Study participants were recruited from shelters, DICs, VCT centers, and street-based venues through outreach efforts. Eligible participants were 18 years or more and self-reported injection drug user for at least once during the previous 12 months. The details of the surveys are previously describe.Our findings showed that as of 2014, less than half of PWID in Iran received OAT in the previous year with significant heterogeneity in OAT uptake across cities. Being ever married, HIV positive, and having a history of incarceration were positively associated with receiving OAT, while using non-opioid drugs were negatively associated with receiving OAT. Moreover, we demonstrated that less than half of the surveyed PWID used OAT in the previous year. Based on the World Health Organization’s definition of high coverage of OAT , Iran falls into the high coverage category. However, there is a high level of disparity for OAT uptake across cities with OAT uptake ranging from 0-75% in different cities. Interestingly,grow table all cities with low OAT coverage were among the less and under developed regions, settings that also have higher rates of child mortality and lower numbers of rehabilitation centers and paramedics in comparison with the rest of the country. Therefore, to reach and maintain the high coverage goal in all regions of the country, allocation of resources regarding the degree of inequality in the distribution of OAT services should be considered in future planning and financing of these services. In addition, addressing and removing the potential barriers to access and use of OAT such as financial barriers, lack of awareness and negative attitudes, worries about methadone’s side effects, and social stigma attached to receiving OAT are integral to increasing the coverage rate of OAT uptake among Iranian PWID. Tackling barriers to OAT access are of particular importance in the context of COVID-19 and future pandemics as accessing such services among PWID is often accentuated during health emergencies. Comparing our results to other countries of the MENA region, the OAT uptake in Iran seems to be higher than most of its neighboring countries. Indeed, the overall OAT provision in MENA is very limited. For example, In 2017, only 7 MENA countries provided OAT which suggests ~ 6% of PWID in the MENA region to be on OAT. However, due to non-random nature of our study sample, these comparisons should be interpreted with caution. The OAT uptake in PWID slightly decreased in 2014 in comparison with 2010. This trend is in opposite direction with the increasing number of facilities that provide OAT services to PWID. Although the observed pattern may be simply due to possible biases in selection of the participants, it might also be due to the recent shift in substance use practices among PWID in Iran and the increase in poly-drug use involving non-opioids among them. Recent studies have shown that methamphetamine use has been increasing among PWID with opioid use disorder.

We also found that compared to PWID who used only opioids within the previous month, those who used only non-opioids and those who used opioids and non-opioids simultaneously, were less likely to have received OAT. Therefore, one possible explanation for the decreasing trend of OAT could be PWID’s increasing tendency toward poly-drug use including stimulants. Following the emergence and increasing supply of synthetic non-opioid drugs including methamphetamines, more PWID tend to use these drugs. On the other hand, the use of methamphetamine in PWID reduces the effectiveness of OAT programs and subsequently leads to lower satisfaction of patients with OAT . These issues are problematic in a way that treatment of PWID who use synthetic drugs has turned into a challenging issue within the last few years. In Iran, there are only a limited number of centers providing treatments for stimulant use disorder. Preliminary studies indicate that the integration of stimulant HR services into opioid HR programs at DICs could be an effective strategy in reducing high-risk behaviors of their clients. Therefore, policies toward the establishment of such centers and providing treatments for stimulant use disorder at DICs should be considered in future policy and planning across the country. Living with HIV was associated with an increased likelihood of OAT uptake, a finding which is consistent with a study conducted in Vancouver, Canada. This may be partly due to the effect of post-test counseling which is freely available for all PWID who undergo HIV testing in Iran. Integration of HIV and substance use services have been shown to improve HIV treatment and care continuum among PWID living with HIV. In our study, having a history of incarceration was positively associated with OAT uptake. This may be due to the establishment of HR programs inside Iran’s prisons. Similar to several international settings, people who use drugs are over represented in prisons across Iran. More than 50% of all Iranian prisoners are being held on drug-related offenses and 70% of them use illicit drugs. When Iran experienced large outbreaks of HIV among incarcerated populations in the early 2000s, HR programs inside prisons were rapidly expanded. As these HR provision and coverage continue to function inside prisons, most PWID with a history of incarceration are likely to have used these services and received OAT during their incarceration period. Previous studies have shown that exposure of prisoners to OAT inside prisons increases their chance of receiving OAT even after their release. Therefore, ensuring the continuation and extension of current strategies of HR inside prisons in Iran is of utmost importance. We acknowledge the limitations of our study. First, social desirability bias may have resulted in over-reporting of OAT uptake and under-reporting of stigmatized and criminalized behaviors such as use of drugs and alcohol. Second, the study was cross-sectional with limited capacity for causal inference. Third, male PWID were over represented in our study sample and our findings may not be generalizable to female PWID in Iran. Fourth, due to non-random selection of the study participants and the possible role of selection bias, the findings might not necessarily represent OAT uptake among all PWID in Iran. Fifth, our data was collected in late 2014 and was delayed in getting published due to several contextual and logistical complexities; therefore, it might not provide a realistic picture of the current status of OAT uptake among PWID in Iran. Lastly, differences in sampling strategy between two study rounds including recruiting participants from different facilities and sites cannot be ruled out as unmeasured confounders, and therefore, comparison between the two rounds should be made with caution.