Objective
To explore the impact of attending a clinical placement in considering a career in obstetrics and gynaecology.
Design
Mixed methods study.
Setting
London Medical School.
Population
Fifth ...year medical students attending a clinical placement in obstetrics and gynaecology.
Methods
Between January 2021 and January 2022, questionnaires were used and semi‐structured focus groups conducted, which were audio‐recorded. Descriptive statistics were conducted and a framework analysis on transcribed focus groups.
Main outcome measure
The impact of the clinical placement on career choice.
Results
Six main themes were identified from the analysis; three contributing to considering a career in obstetrics and gynaecology; pregnancy is not an illness, extraordinary experience of observing childbirth and variable specialty and three themes emerged contributing to not considering a career; lack of work–life balance, high stakes specialty and the emotional toll. Even at an undergraduate level, medical students exhibited concerns about the long‐term feasibility of achieving work–life balance and avoiding professional burnout, which was partly attributed to the responsibility of looking after both the woman and their baby.
Conclusions
Obstetrics and gynaecology is perceived as an exciting and variable speciality by medical students. Students’ experiences on the labour ward during a clinical placement appear to contribute to the consideration of a career in obstetrics and gynaecology. Students should be given opportunities to discuss their concerns about obstetrics, particularly over the potential psychological impact of adverse/traumatic birth events. It is crucial to provide a realistic introduction to obstetrics, to recruit enthusiastic junior doctors who will be resilient to the pressures of the speciality, to avoid burnout and minimise attrition rates.
Linked article: This article is commented on by Charles Weissman, pp.969 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471‐0528.17751.
Aflibercept; a decoy receptor for vascular endothelial growth factors (VEGFs) and placental growth factor (PLGF), in combination with FOLFIRI (leucovorin calcium, fluorouracil, irinotecan ...hydrochloride) chemotherapy regime, was FDA approved in 2012 as second-line salvage chemotherapy for metastatic colorectal cancer (mCRC). This is the first systematic review, and meta-analysis-based evidence to determine the efficacy and safety of Aflibercept plus FOLFIRI regimen pooling randomized controlled trials and single-arm studies.
PubMed, Cochrane library, Embase, and Clinical trial.gov were systematically searched for published randomized controlled trials, single-arm studies, and national patient programs on aflibercept plus FOLFIRI chemotherapy for the treatment of mCRC till 11/10/2022.
Ten studies met the inclusion criteria comprising 1075 patients for efficacy studies and 2027 patients for safety studies. The pooled prevalences were 18% (95% CI, 5%−37%, p = 0.00) for 12 m PFS and 61% (95% CI, 53–68%, p = 0.00) for 12 m OS. The pooled prevalences were 69% (95% CI, 55–82%, p = 0.00) for any grade 3–4 toxicities, 10% (95% CI, 5–16%, p = 0.00) for grade 3–4 diarrhea, 13% (95% CI, 5–24%, p = 0.00) for grade 3–4 hypertension, 31% (95% CI, 22–40%, p = 0.00) for grade 3–4 neutropenia and 5% (95% CI, 2–7%, p = 0.00) for grade 3–4 venous thromboembolic event.
Our meta-analysis shows that the aflibercept plus FOLFIRI combination shows better survival efficacies however; it is also associated with more high-grade adverse events.
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•Targeted VEGF with Aflibercept/FOLFIRI combination has been approved for second-line mCRC after the VELOUR trial.•It shows clinically significant survival efficacies over other combinations.•But also present increased adverse events.•Pooling of the available study based on the therapy represents a better picture of the combination.
Medication Safety Principles and Practice in CKD Whittaker, Chanel F; Miklich, Margaret A; Patel, Roshni S ...
Clinical journal of the American Society of Nephrology,
11/2018, Letnik:
13, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Ensuring patient safety is a priority of medical care because iatrogenic injury has been a primary concern. Medications are an important source of medical errors, and kidney disease is a thoroughfare ...of factors threatening safe administration of medicines. Principal among these is reduced kidney function because almost half of all medications used are eliminated
the kidney. Additionally, kidney patients often suffer from multimorbidity, including diabetes, hypertension, and heart failure, with a range of prescribers who often do not coordinate treatments. Patients with kidney disease are also susceptible to further kidney injury and metabolic derangements from medications, which can worsen the disease. In this review, we will present the key issues and threats to safe medication use in kidney disease, with a focus on predialysis CKD, as the scope of medication safety in ESKD and transplantation are unique and deserve their own consideration. We discuss drugs that need to be avoided or dose modified, and review the complications of a range of medications routinely administered in CKD, as these also call for cautious use.
Alzheimer's disease, a highly prevalent form of dementia, targets neuron function beginning from the hippocampal region and expanding outwards. Alzheimer's disease is caused by elevated levels of ...heavy metals, such as lead, zinc, and copper. Copper is found in many areas of daily life, raising a concern as to how this metal and Alzheimer's disease are related. Previous studies have not identified the common pathways between excess copper and Alzheimer's disease etiology. Our review corroborates that both copper and Alzheimer's disease target the hippocampus, cerebral cortex, cerebellum, and brainstem, affecting motor skills and critical thinking. Additionally, Aβ plaque formation was analyzed beginning from synthesis at the APP parent protein site until Aβ plaque formation was completed. Structural changes were also noted. Further analysis revealed a relationship between amyloid-beta plaques and copper ion concentration. As copper ion levels increased, it bound to the Aβ monomer, expediting the plaque formation process, and furthering neurodegeneration. These conclusions can be utilized in the medical community to further research on the etiology of Alzheimer's disease and its relationships to copper and other metal-induced neurotoxicity.
It is desirable to predict positive food effect of oral formulations due to food mediated dissolution enhancement of lipophilic drugs. The objective was to assess the ability of in vitro lipolysis to ...anticipate a positive food effect. Tested formulations included rivaroxaban and itraconazole, where some formulations, but not all, exhibit a positive food effect in vivo in humans. Amorphous solid dispersion formulations of ritonavir, which exhibit a negative food effect in vivo in humans, were also studied. Fe-lipolysis and Fa-lipolysis media representing fed and fasted intestinal conditions were used. Results show frequent agreement between in vitro lipolysis predictions and in vivo human outcomes. For rivaroxaban, food effect of unformulated active pharmaceutical ingredient (API) and products were correctly predicted where 2.5 mg and 10 mg strengths did not show any food effect; however, 20 mg did show a positive food effect. For itraconazole, all four products were correctly predicted, with Sporanox, Sempera, and generic capsules having a food effect, but Tolsura not having a positive food effect. For ritonavir, lipolysis predicted a positive food effect for API and Norvir tablet and powder, but Norvir products have negative food effect in vivo in humans. Overall, the lipolysis model showed favorable predictability and merits additional evaluation.
Thauera
is the most widely found dominant denitrifying genus in wastewater. In earlier study, MBBR augmented with a specially developed denitrifying five-membered bacterial consortium (DC5) where
...Thauera
was found to be the most abundant and persistent genus. Therefore, to check the functional potential of
Thauera
in the removal of nitrate-containing wastewater in the present study
Thauera
sp.V14 one of the member of the consortium DC5 was used as the model organism.
Thauera
sp.V14 exhibited strong hydrophobicity, auto-aggregation ability, biofilm formation and denitrification ability, which indicated its robust adaptability short colonization and nitrate removal efficiency. Continuous reactor studies with
Thauera
sp.V14 in 10 L dMBBR showed 91% of denitrification efficiency with an initial nitrate concentration of 620 mg L
−1
within 3 h of HRT. Thus, it revealed that
Thauera
can be employed as an effective microorganism for nitrate removal from wastewater based on its performance in the present studies.
Graphical abstract
Background: Flavonoids are plant-based phytochemicals with cardiovascular protective properties. Few studies have comprehensively examined flavonoid classes in relation to cardiovascular disease ...mortality.
Objective: We examined the association between flavonoid intake and cardiovascular disease (CVD) mortality among participants in a large, prospective US cohort.
Design: In 1999, a total of 38,180 men and 60,289 women in the Cancer Prevention Study II Nutrition Cohort with a mean age of 70 and 69 y, respectively, completed questionnaires on medical history and lifestyle behaviors, including a 152-item food-frequency questionnaire. Cox proportional hazards modeling was used to calculate multivariate-adjusted hazard RRs and 95% CIs for associations between total flavonoids, 7 flavonoid classes, and CVD mortality.
Results: During 7 y of follow-up, 1589 CVD deaths in men and 1182 CVD deaths in women occurred. Men and women with total flavonoid intakes in the top (compared with the bottom) quintile had a lower risk of fatal CVD (RR: 0.82; 95% CI: 0.73, 0.92; P-trend = 0.01). Five flavonoid classes—anthocyanidins, flavan-3-ols, flavones, flavonols, and proanthocyanidins—were individually associated with lower risk of fatal CVD (all P-trend < 0.05). In men, total flavonoid intakes were more strongly associated with stroke mortality (RR: 0.63; 95% CI: 0.44, 0.89; P-trend = 0.04) than with ischemic heart disease (RR: 0.90; 95% CI: 0.72, 1.13). Many associations appeared to be nonlinear, with lower risk at intakes above the referent category.
Conclusions: Flavonoid consumption was associated with lower risk of death from CVD. Most inverse associations appeared with intermediate intakes, suggesting that even relatively small amounts of flavonoid-rich foods may be beneficial.
Objective: To evaluate the efficacy, safety, and cost-effectiveness of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and describe its place in therapy for the treatment of ...hypercholesterolemia. Data Sources: A search of MEDLINE, CINAHL, and Clinicaltrials.gov was performed from January 2012 to March 2018 to identify literature pertaining to PCSK9 inhibitors using pre-specified search terms. Additional references were identified from citations of the literature. Study Selection and Data Extraction: Only articles in English were reviewed. Phase II, phase III, pooled, post hoc, and cardiovascular (CV) trials were included. Cost-effectiveness studies and conference materials were also reviewed. Data Synthesis: All trials evaluating alirocumab and evolocumab demonstrated significant low-density lipoprotein cholesterol (LDL-C) lowering versus comparators. Two trials revealed a decrease in the major adverse cardiovascular events (MACE) end point with PCSK9 inhibitor use; 1 of these 2 trials revealed a decrease in all-cause mortality with alirocumab use. No significant safety concerns apart from injection site reactions were noted. Despite these results, 4 cost-effectiveness analyses failed to meet acceptable thresholds. Relevance to Patient Care and Clinical Practice: This review describes the most up-to-date evidence regarding PCSK9 inhibitors. A discussion on LDL-C lowering potential, effect on CV events and mortality, safety considerations, feasibility of administration, and cost are included to guide clinicians on future use. Conclusion: The PCSK9 inhibitor drug class is an effective LDL-C lowering option for patients with the highest risk of CVD events and high LDL-C despite the use of statin therapy. For more widespread use, significant cost reductions are needed.
Biological denitrification is the most promising alternative approach for the removal of nitrate from wastewater. MBBR inoculated with activated sludge is a widely studied approach, but very few ...studies have focused on the bioaugmentation of biofilm forming bacteria in MBBR. Our study revealed that the use of special microbial seed of biofilm forming denitrifying bacteria
Diaphorobacter
sp. R4,
Pannonibacter
sp. V5,
Thauera
sp. V9,
Pseudomonas
sp.V11, and
Thauera
sp.V14 to form biofilm on carriers enhanced nitrate removal performance of developed MBBR. Various process parameters C/N ratio 0.3, HRT 3 h at Nitrate loading 2400 mg L
−1
, Filling ratio 20%, operated with Pall ring carrier were optimized to achieve highest nitrate removal. After 300 days of continuous operation results of whole genome metagenomic studies showed that
Thauera
spp. were the most dominant and key contributor to the denitrification of nitrate containing wastewater and the reactor was totally conditioned for denitrification. Overall, findings suggest that bench-scale MBBR developed with biofilm forming denitrifying microbial seed accelerated the denitrification process; therefore in conclusion it is suggested as one of the best suitable and effective approach for removal of nitrate from wastewater.
There is considerable interest in transplanting stem cells or progenitors into the injured nervous system and enhancing their differentiation into mature, integrated, functional neurons. Little is ...known, however, about what intrinsic or extrinsic signals control the integration of differentiated neurons, either during development or in the adult. Here we ask whether purified, postmitotic, differentiated retinal ganglion cells (RGCs) directly isolated from rat retina or derived from in vitro-differentiated retinal progenitor cells can survive, migrate, extend neurites, and form morphologic synapses in a host retina, in vivo and ex vivo. We found that acutely purified primary and in vitro-differentiated RGCs survive transplantation and migrate into deeper retinal layers, including into their normal environment, the ganglion cell layer (GCL). Transplanted RGCs from a wide range of developmental ages, but not from adults, were capable of extending lengthy neurites in the normal and injured adult rat retina ex vivo and to a lesser degree after transplantation in vivo. We have also demonstrated that RGCs may be differentiated and purified from retinal precursor cultures and that they share many of the same cell biological properties as primary RGCs. We have established that progenitor-derived RGCs have similar capacity for integration as developing primary RGCs but appear to form a lower number of presynaptic punctae. This work provides insight for further understanding of the integration of developing RGCs into their normal environment and following injury.
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