Iatrogenic copper deficiency: Risks and cautions with zinc prescribing.

AIMS: Copper deficiency resulting from prescribing zinc in high doses is a rare but life-changing diagnosis that is frequently overlooked. The aim of this study is to gauge how often zinc-induced copper deficiency is missed, to raise awareness of the condition and to stress the need for guidelines for prescribing zinc. METHODS: Suspected cases of zinc-induced copper deficiency were retrospectively obtained by selecting those patients with hyperzincaemia and hypocupraemia from the database of the Scottish Trace Element Laboratory. Case records were reviewed to determine the validity of the suspected diagnosis. RESULTS: After exclusions, 23 instances of high serum zinc and low serum copper concentrations were found. A positive diagnosis of zinc-induced copper deficiency was made in 14 patients, of which 7 (50%) were previously undiagnosed. CONCLUSION: Serum zinc and copper concentrations are rarely measured in patients prescribed zinc and so the vast majority of cases of zinc-induced copper deficiency are likely to be undiagnosed. We recommend the current official advice on the dose and frequency of zinc administration is revised in order to limit, and potentially eradicate, the condition.

Cumulative and temporal associations between antimicrobial prescribing and community-associated Clostridium difficile infection: population-based case-control study using administrative data.

Background: Community-associated Clostridium difficile infection (CA-CDI; defined as cases without prior hospitalization in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescribing of antimicrobials in primary care and CA-CDI. Methods: Three national patient-level datasets, covering CDI cases, community prescriptions and hospitalizations, were linked by the NHS Scotland unique patient identifier, the Community Health Index (CHI). All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression. Results: The 1446 unique cases of CA-CDI were linked with 7964 age-, sex- and location-matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with more than 28 DDDs to any antimicrobial (19.9% of cases) had an OR of 4.4 (95% CI 3.4-5.6) compared with those unexposed. Individuals exposed to 29+ DDDs of high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR of 17.9 (95% CI 7.6-42.2). Elevated CA-CDI risk following high-risk antimicrobial exposure was greatest in the first month (OR = 12.5, 95% CI 8.9-17.4), but was still present 4-6 months later (OR = 2.6, 95% CI 1.7-3.9). Cases exposed to 29+ DDDs had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long-term prophylactic use. Conclusions: This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials, with an impact of exposure to high-risk antimicrobials remaining 4-6 months later.

Awareness and attitudes of oncology specialists toward dihydropyrimidine dehydrogenase testing in Saudi Arabia.

BACKGROUND: Fluoropyrimidines (FP) are among the most common class of prescribed anti-neoplastic drugs. This class has severe to moderate toxicity in around 10%-40% of those who take 5-fluorouracil (5-FU) or capecitabine for the treatment of cancer. In practice many patients with severe toxicities from FP use had dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. Several studies have proposed DPD screening before treatment with 5-fluorouracil (5-FU) and capecitabine or other drugs belonging to the FP group. This study aims to assess the level of awareness and attitudes of oncology specialists in Saudi Arabia toward genetic screening for DPD prior to giving FP. This highlights the importance of health guidelines required for implementation in our health care system, as a framework to adopt testing as a regular practice in clinical care. Based on the findings in this study, guidelines have been suggested for the Middle East North Africa region. METHODS: A cross-sectional survey study was conducted during 2021 targeting oncologists and clinical pharmacists working in the oncology departments across Saudi Arabia. RESULTS: A total of 130 oncologists and pharmacists completed the questionnaire representing a response rate of 87%. Most of the respondents indicated that they prescribe FP in clinical practice, but 41% of respondents reported that they have never ordered a specific molecular test during their practice. Only 20% of respondents reported that they often screen for DPD deficiency prior to prescribing FP. Significantly higher rates of awareness of potential dihydropyrimidine dehydrogenase gene (DPYD) mutation were observed among respondents in governmental hospitals (81.1% vs. 47.4% in private hospitals), and among those with more years of practice (80.6% if 5 or more years of practice vs. 59.3% if less than 5 years of practice). Also, higher rates of observing the impact of DPD testing were present among respondents with a PharmD (35% vs. 11% for oncologists and 18% for other professions) and among those with 5 or more years of practice (24.6% vs. 7.7% among those with less than 5 years). CONCLUSION: While in some institutions there is a high level of awareness among oncology specialists in Saudi Arabia regarding the effect of the potentially serious DPD enzyme deficiency as a result of gene mutations, screening for these mutations prior to prescribing FP is not a routine practice in hospitals across the country. The findings of this study should promote personalized medicine with recognition of interpatient variability via DPD testing to manage the risks of FP prescribing more effectively in the Kingdom of Saudi Arabia.

The law of unintended consequences: The Joint Commission regulations and the digital rectal examination.

STUDY OBJECTIVE: The Joint Commission (TJC) recently issued stringent regulations about quality control testing of waived laboratory tests. Many hospitals subsequently instituted detailed procedures for performing, evaluating, documenting, and tracking point-of-care testing for fecal occult blood testing. We hypothesize that implementing this policy would generate an "opportunity cost" because busy physicians would need to compensate for this additional time required by reducing the frequency of digital rectal examinations or fecal occult blood testing. METHODS: We designed a before/after study to measure use of digital rectal examination and fecal occult blood testing in a single-center study between 2002 and 2003. The experimental intervention was implementation of TJC-based hospital policy requiring physicians to manually document fecal occult blood testing quality control data. Charts were screened for 6 a priori established index diagnoses: abdominal pain, gastrointestinal bleeding, chest pain, constipation, diarrhea, and syncope/presyncope. Trained data extractors recorded the presence or absence of digital rectal examination and fecal occult blood testing by using explicit medical record review methods, and rates of both digital rectal examination and fecal occult blood testing were calculated. RESULTS: We screened 3,337 charts and 788 met our inclusion criteria. For the primary outcome, physicians performed 16.7% fewer digital rectal examinations after implementation of the policy (41.3% versus 24.6%). Fecal occult blood testing decreased by 18.7% (38.5% versus 19.8%). CONCLUSION: TJC-inspired point-of-care testing policy was negatively and unintentionally associated with physician examinations, most notably the performance of a digital rectal examination. Institutional regulations designed for patient safety may unintentionally influence patient care. Economists describe this paradoxic phenomenon as the Law of Unintended Consequences. The costs and benefits of such policies should be analyzed before implementation and enforcement of new medical regulations.

Antibiotic treatment of urinary tract infection by community pharmacists: a cross-sectional study.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common conditions seen in female patients within primary care. Community pharmacists are familiar with symptomatic UTI management and supplying trimethoprim under patient group direction (PGD) for moderate-to-severe uncomplicated UTIs could improve patient access to treatment. AIM: To compare the care pathway of patients with UTI symptoms attending GP services with those receiving management, including trimethoprim supply under PGD, via community pharmacies. DESIGN AND SETTING: Prospective, cross-sectional, mixed methods approach in 10 community pharmacies within NHS Greater Glasgow and Clyde. METHOD: Pharmacies invited a purposive sample of female patients to participate. Pharmacists had the option of supplying trimethoprim under PGD to patients with moderate-to-severe infection meeting the PGD inclusion criteria. Data from patient (questionnaires and semi-structured telephone interviews) and pharmacist (questionnaires and semi-structured, face-to-face interviews) were quantitatively and qualitatively analysed. RESULTS: Data were recorded on 153 patients, 97 presenting with GP prescriptions and 56 presenting directly in the pharmacy with symptoms suggestive of UTI, of whom 41 received trimethoprim via PGD and 15 received symptomatic management. Both GP adherence to local infection management guidelines and pharmacist application of PGD inclusion/exclusion criteria required improvement. There was demand and support, from patients and pharmacists, for access to antibiotic treatments for UTIs, without prescription, through community pharmacies. CONCLUSION: Operating within PGD controls, antibiotic treatments for UTIs could be provided via community pharmacy to improve patient access to treatment which may also maintain antibiotic stewardship and reduce GP workload.

Systemic Par-4 inhibits non-autochthonous tumor growth.

The tumor suppressor protein Par-4 (Prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SAC domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SAC has not been validated in animal models. We show that Par-4/SAC-transgenic mice express systemic Par-4/SAC protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SAC pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SAC protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SAC is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy.

Comparison of methanol exposure routes reported to Texas poison control centers.

OBJECTIVE: Methanol poisoning by ingestion is well represented in current emergency medicine literature. Much less described, however, is poisoning via intentional inhalation of methanol-containing products such as carburetor cleaner. This study intends to explore the exposure routes and treatment patterns of methanol cases reported to Texas Poison Centers. METHODS: All cases of methanol exposures from January 2003 to May 2005 were collected from the Texas Poison Center Network database "Toxicall." Inclusion criteria were 1) methanol as primary exposure, and 2) documented route of exposure. Exclusion criteria were unknown, dermal, and eye exposures. Data was extracted from documented calls to Texas Poison Centers and analyzed using descriptive statistics. RESULTS: A total of 203 cases were collected from 6 regional Poison Centers. Eighty seven cases had inhalation as the route of exposure, while 81 were methanol ingestions. Carburetor cleaner was responsible for nearly all the inhalational cases (79/87) while ingestions involved mostly windshield washer fluid (39/81) and carburetor cleaner (20/81). Seventy-eight percent of the inhalational exposures were intentional while most of the ingestions were accidental (49/75) and suicidal (18/75). An anion gap was documented in 31 of the inhalational cases and in 10 of the ingestions. Dialysis, use of fomepizole, and vision loss were documented for both types of exposure. Fifty-six percent of the inhalational group was admitted compared to 46% of the ingestion group. CONCLUSION: We propose that the results obtained from our review show inhalational exposure involving methanol (e.g., "huffing") represents a significant source of toxicity in the studied population. This is in contrast to previous literature that proposed inhalational toxicity was rare and aggressive treatment usually not necessary in cases of inhalation of methanol-containing carburetor cleaners.