Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world’s rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.

Pulmonary hypertension in the setting of cirrhosis and portal hypertension is known as portopulmonary hypertension (PPHTN). Moderate or severe PPHTN is uncommon, but has a poor prognosis and is considered to be a contraindication to liver transplantation. We assessed the impact of vasodilation therapy on pulmonary hemodynamics and outcome after liver transplant in these patients. Eighty-six patients evaluated for liver transplant between 1997 and 2005 had an estimated right ventricular systolic pressure >40 mm Hg or a clinical suspicion of PPHTN. Right heart catheterization confirmed PPHTN in 30 patients (ten mild, eight moderate, and 12 severe). Sixteen of the 20 with moderate-to-severe pulmonary hypertension (mPAP ≥ 35) were otherwise considered suitable liver transplant candidates and were treated with vasodilation therapy. mPAP fell to less than 35 mm Hg in 12 patients (75%) and 11 of them then underwent orthotopic liver transplantation. One-and five-year survivals in the transplanted patients were 91% and 67%, respectively. Nine of 11 were off vasodilator therapy after a median of 9.2 months following transplantation. None of the patients who failed vasodilator therapy survived (median survival, 8 months). Effective pharmacologic control of PPHTN before liver transplant is associated with excellent posttransplant survival that is similar to patients transplanted for other indications.

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Valproate (2-propylpentanoate) is available as valproic acid, sodium valproate and semisodium valproate. It has actions on dopamine, GABA and glutamate neurotransmission and intracellular signaling. Its main psychiatric use is to treat bipolar disorder. It has been used in other psychiatric disorders, including schizophrenia and borderline personality disorder, but data are insufficient to recommend this. In acute mania, valproate monotherapy has similar efficacy to antipsychotic drugs and lithium whereas the combination of valproate and an antipsychotic is more effective than either drug alone. In maintenance treatment of bipolar disorder, valproate monotherapy has comparable efficacy to olanzapine although placebo-controlled evidence is limited. Maintenance treatment with valproate and quetiapine or olanzapine is more efficacious than valproate alone when an acute episode responds to the combination. Common adverse effects of valproate include weight gain, gastrointestinal symptoms, sedation, tremor and mild elevation of hepatic enzymes. Serious hepatic toxicity is rare in adults. Many adverse effects are dose related and resolve with dose reduction. Valproate is teratogenic and specifically associated with neural tube defect. Preliminary evidence has linked in utero exposure to decreased verbal intelligence in the offspring. These effects, plus a probable increased risk of polycystic ovary syndrome, limit valproate's use in women of childbearing potential.

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Due to the well-known endocrine disrupting ability of bisphenol A (BPA), its production and usage have been regulated. Consequently, other bisphenol analogues (BPs) have been used as the replacement of BPA. Despite their widespread use, few studies have investigated the occurrence and fate of BPs in wastewater treatment plants (WWTPs). In this study, we conducted a city-wide monitoring survey and collected the wastewater and sludge samples from seven WWTPs in Xiamen, China over seven days. The concentrations of dissolved and adsorbed BPs in the influent and effluent, together with the BP concentrations in the sludge were determined. Five BPs, including BPA, BPAF, BPE, BPF, and BPS, were widely detected. The medium concentrations of BPA, BPAF, BPE, BPF, and BPS were 1318, 0.282, 3.70, 50.0, and 48.0 ng/L in the influent, 177, 0.714, 3.64, BLD, and BLD in the effluent, and 343, 3.09, BLD, 56.5, 1.01 μg/kg in the sludge. Spatial variations were observed, which implied the industrial origin of BPA. The efficiencies of BP removal from aqueous phase were evaluated, and results showed that BPA, BPF, and BPS were highly removed with removal efficiencies higher than 78%, while BPAF and BPE were resistant in WWTPs. Mass load calculations showed that 2075 g BPs entered into the WWTPs in Xiamen City each day, while 246 g and 63 g were discharged via effluent and excess sludge, respectively. Mass balance analysis showed that BPS and BPA were mainly biodegraded, BPF were mainly adsorbed and biodegraded, BPAF was resistant to biodegradation, while BPE was resistant to both biodegradation and adsorption.

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