The number of prescribed medications can be an index of PIM risk in older patients with chronic diseases. Clinicians should suspect high PIM risk in older outpatients with ≥ 5 prescriptions.

This retrospective analysis compared the efficiency of the gonadotropin- releasing hormone (GnRH) antagonist (GnRH-ant) protocol and the GnRH agonist long (GnRH-a) protocol for patients with diminished ovarian reserve (DOR). A total of 1,233 patients with DOR (anti-Mullerian hormone <1.1 ng/mL) were recruited for this retrospective case-control study. They were divided into two groups according to female age. Younger patients were assigned to POSEIDON group3 (PG3: age ≤35 years); older patients were assigned to POSEIDON group 4 (PG4: age >35 years). All patients with DOR underwent controlled ovarian stimulation and fresh embryo transfer (ET) on day 3. We recruited 283 GnRH-a and 54 GnRH-ant cycles for PG3, and 663 GnRH-a and 233 GnRH-ant cycles for PG4. In PG3, the GnRH-a protocol was associated with a lower ET cancellation rate (30/283 = 10.2% vs. 12/54 = 22.2%, p = 0.018) and a higher live birth rate (7/54 = 13.0% vs. 78/283 = 27.6%, p = 0.024) than the GnRH-ant protocol for the initiated cycles. Furthermore, the GnRH-a protocol was correlated with a higher implantation rate than the GnRH-ant protocol for ET cycles (146/577 = 25.3% vs. 11/103 = 10.7%, P = 0.027). No differences in the ET cancellation rate, live birth rate and implantation rate between GnRH-a and GnRH-ant groups were observed among PG4 patients. In conclusion, the GnRH-a protocol was more effective than the GnRH-ant protocol for young patients with DOR. The low ET cancellation rate and high implantation rate may be related to embryo quality or endometrial receptivity, which warrant further investigation.

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Small-molecule compounds that target mismatched base pairs in DNA offer a novel prospective for cancer diagnosis and therapy. The potent anticancer antibiotic echinomycin functions by intercalating into DNA at CpG sites. Surprisingly, we found that the drug strongly prefers to bind to consecutive CpG steps separated by a single T:T mismatch. The preference appears to result from enhanced cooperativity associated with the binding of the second echinomycin molecule. Crystallographic studies reveal that this preference originates from the staggered quinoxaline rings of the two neighboring antibiotic molecules that surround the T:T mismatch forming continuous stacking interactions within the duplex. These and other associated changes in DNA conformation allow the formation of a minor groove pocket for tight binding of the second echinomycin molecule. We also show that echinomycin displays enhanced cytotoxicity against mismatch repair-deficient cell lines, raising the possibility of repurposing the drug for detection and treatment of mismatch repair-deficient cancers.

Objective: To evaluate the prescription of potentially inappropriate medications (PIM), using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and Beers criteria, to disabled older people. Subjects and Methods: One hundred and forty-one patients aged ≥65 years with Barthel scale scores ≤60 and a regular intake of medication for chronic diseases at Chung Shan Medical University Hospital from July to December 2012 were included, and their medical records were reviewed. Comprehensive patient information was extracted from the patients' medical notes. The STOPP and Beers 2012 criteria were used separately to identify PIM, and logistic regression analyses were performed to identify risk factors for PIM. The optimal cutoff for the number of medications prescribed for predicting PIM was estimated using the Youden index. Results: Of the 141 patients, 94 (66.7%) and 94 (66.7%) had at least one PIM identified by the STOPP and Beers criteria, respectively. In multivariate analysis, PIM identified by the Beers criteria were associated with the prescription of multiple medications (p = 0.013) and the presence of psychiatric diseases (p < 0.001), whereas PIM identified by the STOPP criteria were only associated with the prescription of multiple medications (p = 0.008). The optimal cutoff for the number of medications prescribed for predicting PIM by using the STOPP or Beers criteria was 6. After adjustment for covariates, patients prescribed ≥6 medications had a significantly higher risk of PIM, identified using the STOPP or Beers criteria, compared to patients prescribed <6 medications (both p < 0.05). Conclusion: This study revealed a high frequency of PIM in disabled older patients with chronic diseases, particularly those prescribed ≥6 medications.