Levothyroxine may not adequately prepare hypothyroid women for controlled ovarian hyperstimulation.

BACKGROUND: Thyroid axis dysregulation during controlled ovarian hyperstimulation (COH) is more pronounced in hypothyroid-treated women. Whether or not this leads to compromised thyroid hormone levels within the ovarian follicular fluid is not known. AIMS: To determine whether ovarian follicular thyroid hormone levels are compromised in adequately replaced hypothyroid women undergoing controlled ovarian hyperstimulation (COH), and/or influence cycle/pregnancy outcomes. MATERIALS AND METHODS: Prospective cohort study involving 46 euthyroid (anti-thyroid peroxidase antibody negative) and 16 levothyroxine-replaced women with baseline thyroid-stimulating hormone (TSH) <2.5 mIU/L attending their first COH cycle. Follicular fluid TSH, free triiodothyronine (T3) and free thyroxine (T4) were recorded at oocyte pick-up. Serum levels were measured at: (i) baseline; (ii) human chorionic gonadotropin trigger day; and (iii) cycle conclusion. The number of mature oocytes retrieved, fertilisation, early pregnancy loss and live birth rates were compared. RESULTS: Median serum TSH levels were similar at baseline (1.76 vs 1.24 mIU/L, P = 0.053), but free T3 levels were lower (4.5 vs 4.8 pmol/L, P = 0.029) in levothyroxine-replaced compared to euthyroid women, with serum TSH levels increasing across ovarian stimulation (P = 0.006) into pregnancy testing (P = 0.030). Follicular fluid free T3 levels were lower in levothyroxine-replaced women (median 4.3 vs 4.6 pmol/L, P = 0.032). Fertilisation rates were lower (52% vs 71%, P = 0.043) in women requiring levothyroxine replacement, but numbers of mature oocytes retrieved, early pregnancy loss and live births did not differ. CONCLUSION: Adequately replaced hypothyroid women achieve lower ovarian follicular fluid free T3 levels and poorer fertilisation rates compared to euthyroid women undergoing COH. Optimising T3 levels may be pivotal in improving COH outcomes in hypothyroid women.

Successful live birth following a short course of glucocorticoid suppression in a patient with autoimmune polyglandular syndrome type 2 and premature ovarian insufficiency: A case report.

A 32-year-old nulliparous woman with premature ovarian insufficiency POI and autoimmune polyglandular syndrome type 2 (APS-2), presented to our fertility center with a 2.5-year history of amenorrhoea. Controlled ovarian hyperstimulation (COH), with high dose gonadotropins, failed to promote antral follicle growth. The patient was given a short, 4-week course of 2 mg dexamethasone prior to a repeat COH cycle, which resulted in the retrieval of good oocyte numbers and eventual live birth from a thawed embryo transfer.

Prior iodine exposure and impact on thyroid function during controlled ovarian hyperstimulation: A prospective study.

AIMS: Iodine supplements are recommended for women planning pregnancy, but their impact on thyroid function during controlled ovarian hyperstimulation (COH) and into pregnancy is unknown. The aim of this study was to assess the impact of iodine supplementation on thyroid function during COH. METHODS: One-hundred and six euthyroid women (thyroid stimulating hormone (TSH) 0.4-2.5 mIU/L) planning their first COH cycle were subdivided according to iodine supplementation (nil, <6 months, ≥6 months) and compared to levothyroxine (LT4)-treated controls. Serial TSH, free thyroxine, free triiodothyronine and thyroglobulin (Tg) levels were recorded at four time points: (i) baseline, (ii) day 7 ovarian stimulation, (iii) ovulation trigger and (iv) two weeks post oocyte retrieval. Oocyte numbers, fertilisation rates and pregnancy outcome were recorded. RESULTS: TSH increased during COH for those women taking iodine supplements for ≥6 months (P = 0.025). One quarter recorded a TSH level >2.5 mIU/L before embryo transfer. A similar increase in TSH was demonstrated by LT4-dependent controls (P = 0.024) but not the remaining subgroups. Tg levels did not change during COH in any group but decreased significantly post oocyte retrieval if nil iodine (P < 0.0001) or supplemented for ≥6 months (P < 0.005). Iodine supplementation did not influence oocyte count, fertilisation or implantation rates. Women taking iodine for <6 months were four times more likely to achieve a live birth than women taking iodine for longer. CONCLUSIONS: Women taking iodine supplements for ≥6 months are less able to adapt to the thyroidal demands of COH, with responses comparable to LT4-dependent patients.

Ovulatory disorders are an independent risk factor for pregnancy complications in women receiving assisted reproduction treatments.

BACKGROUND: Conception using assisted reproduction treatments (ART) has been associated with an increased risk of pregnancy complications. It is uncertain if this is caused by ART directly, or is an association of the underlying factors causing infertility. AIMS: We assessed the relationship between assisted conception (AC) and maternal or fetal complications in a large retrospective cohort study. In a nested cohort of women receiving infertility treatment, we determined if such risk rests predominantly with certain causes of infertility. MATERIALS AND METHODS: Retrospective database analysis of 50 381 women delivering a singleton pregnancy in four public hospital obstetric units in western Sydney, and a nested cohort of 508 women receiving ART at a single fertility centre, in whom the cause of infertility was known. RESULTS: A total of 1727 pregnancies followed AC; 48 654 were spontaneous conceptions. Adjusted for age, body mass index and smoking, AC was associated with increased risk of preterm delivery (OR 1.73, 95% CI 1.50-2.02), hypertension (OR 1.55, 95% CI 1.34-1.82) and diabetes (OR 1.51, 95% CI 1.30-1.75). In the nested cohort, ovulatory dysfunction was present in 145 women and 336 had infertility despite normal ovulatory function. Ovulatory dysfunction was associated with increased risk of diabetes (OR 2.94, 95% CI 1.72-5.02) and hypertension (OR 2.40, 95% CI 1.15-5.00) compared to women with normal ovulatory function. CONCLUSIONS: Assisted conception is associated with increased risk of pregnancy complications. This risk appears greatest for women whose underlying infertility involves ovulatory dysfunction. Such disorders probably predispose towards diabetes and hypertension, which is then exacerbated by pregnancy.

Elevated anti-Mullerian hormone in lean women may not indicate polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a heterogeneous disorder with clinical features shared with functional hypogonadotrophic hypogonadism (FHH). AIM: To investigate the usefulness of an elevated (>40 pmol/L) anti-Mullerian hormone (AMH) in identifying PCOS and distinguishing PCOS from FHH. MATERIALS AND METHODS: 141 patients with an elevated AMH and body mass index either <20 kg/m2 (lean) or >30 kg/m2 (obese) were selected and three subgroups analysed - obese, lean, lean with suspected FHH. FHH was diagnosed clinically, incorporating diet, weight and exercise history; confirmatory tests included pituitary MRIs, progestin challenges and endometrial thickness measurements. PCOS features of oligo/anovulation, polycystic ovarian morphology (PCOm) and hyperandrogenism were determined by clinical history, pelvic ultrasound, free androgen index and physical examination, respectively. Features of PCOS and blood levels of AMH, follicle-stimulating hormone, luteinising hormone, sex hormone binding globulin (SHBG) and testosterone were compared between subgroups. RESULTS: Of 141 patients with elevated AMH, 76 were obese and 65 lean. Greater than one-third of lean women had the clinical picture of FHH. Elevated AMH predicted PCOm and menstrual irregularity across all subgroups but uniquely associated with hyperandrogenism in the obese. Median AMH levels were similar among FHH and non-FHH women. Median SHBG levels were significantly higher (111 ± 73 vs 56 ± 31, P < 0.001) in lean women with FHH compared to those without FHH. CONCLUSIONS: PCOS and FHH share common features of elevated AMH levels, oligo-anovulation and polycystic ovarian morphology. AMH did not assist in differentiating FHH from PCOS. A higher SHBG level shows promise as a discriminatory finding in FHH.

Capsaicin-based therapies for pain control.

The TRPV1 receptor is known to play a role in nociceptive transmission in multiple organ systems, usually in response to the pain of inflammation. TRPV1 antagonism has so far shown limited benefit in antinociception. Capsaicin, a TRPV1 agonist, has been shown to induce a refractory period in the nerve terminal expressing TRPV1 and even, in sufficient dosing, to create long-term nerve terminal defunctionalization. This has led to research into topical capsaicin as a treatment for multiple painful conditions. The majority of work has focused on musculoskeletal pain and neuropathic pain and has revealed that although low-dose topical capsaicin has limited effectiveness as an analgesic, high-dose capsaicin, when tolerated, has the potential for long-term analgesia in certain types of neuropathic pain.

Painful boney metastases.

Up to 90% of patients with metastatic or advanced stage cancer will experience significant cancer-related pain. Approximately half or more of patients diagnosed with cancer may experience bone pain. It has been estimated that tumor metastases to the skeleton affects roughly 400,000 US citizens annually. Carcinoma from breast, lung, and prostate cancers account for approximately 80% of secondary metastatic bone disease. Bone metastases may cause devastating clinical complications associated with dramatic reductions in quality of life, mobility, and independence, as well as excruciating refractory pain. Associated complications from osseous metastases also present a substantial economic burden. Currently, there are still a significantly high number of patients suffering with unrelieved pain from osseous metastases. Treatments for painful osseous metastases may not only diminish pain but also may improve quality of life and independence/mobility, and reduce skeletal morbidity, potential pathologic fractures, spinal cord compression, and other "skeletal-related events." Treatment strategies for painful osseous metastases include the following: systemic analgesics, intrathecal analgesics, glucocorticoids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation and cryoablation), bisphosphonates, chemotherapeutic agents, inhibitors of RANKL-RANK interaction (eg, denosumab), hormonal therapies, interventional techniques (eg, kyphoplasty), and surgical approaches. Although the mechanisms underlying the development of bone metastases remain incompletely understood, there appears to be important bi-directional interactions between the tumor and the bone microenvironment. A greater understanding of the pathophysiology of painful osseous metastases may lead to better and more selective targeted analgesic therapy. Additionally, potential future therapeutic approaches to painful osseous metastases may revolutionize approaches to analgesia for this condition, leading to optimal outcomes with maximal pain relief and minimal adverse effects.

Cervical radicular pain: the role of interlaminar and transforaminal epidural injections.

Chronic neck pain and cervical radicular pain are relatively common in the adult population. Treatment for chronic radicular pain recalcitrant to conservative management includes surgical management as well as interventional techniques with epidural injections utilizing either an interlaminar approach or transforaminal approach. Although there have been multiple systematic reviews and randomized clinical trials of cervical interlaminar epidural injections, the literature is sparse in reference to cervical transforaminal epidural injections. Overall, there is good evidence for the effectiveness of cervical interlaminar epidural injections in managing cervical disc herniation and fair evidence in managing central spinal stenosis and postsurgery syndrome. The evidence is poor, however, for cervical transforaminal epidural injections. Complications with cervical interlaminar epidural injections are rare, but more commonly occur with transforaminal epidural injections and can be fatal. Emerging concepts in pain include further randomized trials; proper placebo design; focus on control design (either active control or placebo control); and appropriate methodologic quality assessment and evidence synthesis.

Revision of an Adult Burn Center's Resuscitation Guideline Leads to Lower Resuscitation Requirements.

In 2018, the institutional burn resuscitation guideline was updated to remove the use of high-dose ascorbic acid (HDAA) therapy, to lower 24-hour resuscitation fluid estimations from 4 to 2 mL/kg/TBSA, and to optimize guidance around appropriate colloid resuscitation. This retrospective study compared the incidence of a composite safety outcome (acute kidney injury, or intra-abdominal hypertension requiring intervention) between the pre-guideline update to post-guideline update. Secondarily, 24-hour resuscitation volumes, hourly urine output, vasopressor use, and mechanical ventilation duration were compared as well. The composite safety outcome was similar between the 2 groups (40% vs 29%; p=0.27), but the post-group showed significantly lower 24-hour resuscitation volumes (3.74 mL/kg/TBSA vs 2.94 mL/kg/TBSA; p<0.01), as well as lower urine output (1.26 mL/kg/hr vs 0.75 mL/kg/hr; p<0.01). There was no difference between the groups with respect to vasopressor use, mechanical ventilation duration, or mortality. This study suggests that a simplified resuscitation protocol without HDAA, combined with a lower starting fluid rate led to significantly lower 24-hour resuscitation volumes without an increase in adverse safety events.

Optimizing Nutritional Needs of Burn Patients: An Evaluation of Nutritional Assessment Tools, Feeding Strategies, and Their Impact on Patient Outcomes.

BACKGROUND: Optimal nutritional support is essential to the recovery and improved outcomes of burn patients. This review aims to explore existing literature to evaluate nutrition assessment tools, feeding formulations' caloric predictive ability, timing of initiation of feeding, optimal nutritional composition, and caloric intake in burn patients. METHODS: Three databases were searched to glean studies investigating nutrition in acute severe adult burn patient populations in four areas: outcomes based on feeding type and timing, the caloric predictability of nutritional assessment tools, outcomes associated with the composition of feeding formulas, and considerations related to caloric intake. Outcomes of interest included the effects of nutritional assessments using feeding type, nutritional administration timing, formula composition, and caloric intake on mortality rate, length of stay, and infection. RESULTS: A total of 19 studies were included. Nutritional assessment tools were determined to over- or underestimate resting energy expenditure (REE). Milner was the most accurate alternative to indirect calorimetry. Early enteral nutrition in burn patients within 24 hours of admission was preferred. 5 studies evaluated micronutrients and yielded variable results. Low-fat high-carbohydrate diets were the ideal macronutrient composition. Burn patients were shown to receive lower caloric intake than recommended. CONCLUSIONS: Findings showed that while nutritional assessment tools tend to inaccurately estimate REE in burn patients, the ideal alternative to indirect calorimetry is the Milner equation. Several new equations may be worthy alternatives but require further validation. Enteral feeding should be initiated within the first 24 hours of burn injury whenever possible and should contain a high-carbohydrate/low-fat composition.

The spectrum of systemic sclerosis-associated pulmonary hypertension: Insights from the ASPIRE registry.

BACKGROUND: There are limited data assessing the spectrum of systemic sclerosis-associated pulmonary hypertension (PH). METHODS: Data for 912 systemic sclerosis patients assessed between 2000 and 2020 were retrieved from the Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre (ASPIRE) registry and classified based on 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines and multimodality investigations. RESULTS: Reduction in pulmonary vascular resistance (PVR) diagnostic threshold to >2WU resulted in a 19% increase in precapillary PH diagnoses. Patients with PVR ≤2WU had superior survival to PVR >2-3WU which was similar to PVR >3-4WU. Survival in pulmonary arterial hypertension (PAH) was superior to PH associated with lung disease. However, patients with mild parenchymal disease on CT had similar characteristics and outcomes to patients without lung disease. Combined pre- and postcapillary PH had significantly poorer survival than isolated postcapillary PH. Patients with mean pulmonary arterial wedge pressure (PAWP) 13-15 mm Hg had similar haemodynamics and left atrial volumes to those with PAWP >15 mm Hg. Unclassified-PH had more frequently dilated left atria and higher PAWP than PAH. Although Unclassified-PH had a similar survival to No-PH, 36% were subsequently diagnosed with PAH or PH associated with left heart disease. The presence of 2-3 radiological signs of pulmonary veno-occlusive disease was noted in 7% of PAH patients and was associated with worse survival. Improvement in incremental shuttle walking distance of ≥30 m following initiation of PAH therapy was associated with superior survival. PAH patients diagnosed after 2011 had greater use of combination therapy and superior survival. CONCLUSION: A number of systemic sclerosis PH phenotypes can be recognized and characterized using haemodynamics, lung function and multimodality imaging.

Buprenorphine in the treatment of non-suicidal self-injury: a case series and discussion of the literature.

A global public health problem, non-suicidal self-injury (NSSI) is highly prevalent in both males and females, and tends to first occur in adolescence. NSSI is correlated with a history of childhood trauma, and with a variety of developmental and psychiatric disorders. NSSI is associated with increased risk of morbidity and premature death from suicide, accidents, and natural causes. Current treatment approaches are inadequate for a substantial number of people. Converging evidence for opioid system dysregulation in individuals with NSSI make this a promising area of investigation for more effective treatments. The pharmacological profile of buprenorphine, a potent µ-opioid partial agonist and κ-opioid antagonist, suggests that it may be beneficial. In this paper, we describe the successful treatment of severe NSSI with buprenorphine in six individuals, followed by discussion and further recommendations.

Relationship Between Preexisting Functional Mobility Impairments and Burn Treatment Outcomes.

Burn severity is determined by total body surface area affected, temperature of source, and duration of exposure. Patients with impaired mobility are less capable of avoiding hazards and escaping traumatic injuries. Additionally, patients with impaired mobility frequently suffer from other comorbid conditions and have specialized needs, which can complicate their acute treatment. This study was a retrospective electronic medical records review of all adult patients, aged 18 years and older with a preexisting mobility impairment, admitted as inpatients to a single burn center for treatment of burn-related injuries from January 1, 2009, to December 31, 2019. The 10-year review of 1520 adult burn admissions meeting the initial criteria of inpatient admission and burn injury revealed 174 patients with documentation supporting preexisting functional mobility impairment (11%). Surprisingly, patients' overall lengths of stays were consistent with all burn populations at 0.81 days per % TBSA, with the average length of stay being 6.7 days. The demographic data were consistent with national burn registry data as male, Caucasian, and older, with mean age of 61.1 years. Demographic data and details of hospital course focusing on treatment, complications, and outcomes were extracted and analyzed. There is a paucity of literature describing the needs of this unique burn population. Burn-injured patients with preexisting mobility impairments suffer from similar mechanisms of injury. By identifying attributes unique to this population, we hope to develop specialized prevention education and treatment protocols.

'The dark before the dawn': the 2021 British Thoracic Society Audit of the treatment of tobacco dependency in acute trusts.

Smoking remains the single largest cause of preventable death, disability and health inequality. Smoking tobacco directly contributes to over 500 000 hospital admissions each year, making hospitals an important location to optimise treatment for tobacco dependency. The third British Thoracic Society Tobacco Dependency Audit was undertaken to determine how effectively national standards for treating tobacco-dependent smokers have been implemented and assess if any progress has been made from previous audits. Data on 14579 patients from 119 hospitals revealed 21% of patients were current smokers, 45% were offered very brief advice and 5% prescribed combination nicotine replacement therapy or varenicline. Only 9% completed a consultation with a specialist tobacco dependency practitioner during their inpatient stay and fewer than 1% of smokers were abstinent at 4 weeks following discharge. Clinical leadership of tobacco dependency services was deficient, and staff were ill equipped in supporting current smokers in their efforts to quit with only 50% of trusts offering regular smoking cessation training. There has been little meaningful improvement from previous audits and there remains woefully inadequate provision of tobacco dependency treatment for patients who smoke. The National Health Service (NHS) Long Term Plan has committed substantial, new funding to the NHS to ensure every patient that smokes admitted to hospital will be offered evidence-based support and treatment for tobacco dependency. The findings of this audit highlight the urgency with which this programme must be implemented to tackle the greatest cause of premature death in the UK and to achieve the wider well-recognised benefits for the healthcare system.

Prediction on X-ray output of free electron laser based on artificial neural networks.

Knowledge of x-ray free electron lasers' (XFELs) pulse characteristics delivered to a sample is crucial for ensuring high-quality x-rays for scientific experiments. XFELs' self-amplified spontaneous emission process causes spatial and spectral variations in x-ray pulses entering a sample, which leads to measurement uncertainties for experiments relying on multiple XFEL pulses. Accurate in-situ measurements of x-ray wavefront and energy spectrum incident upon a sample poses challenges. Here we address this by developing a virtual diagnostics framework using an artificial neural network (ANN) to predict x-ray photon beam properties from electron beam properties. We recorded XFEL electron parameters while adjusting the accelerator's configurations and measured the resulting x-ray wavefront and energy spectrum shot-to-shot. Training the ANN with this data enables effective prediction of single-shot or average x-ray beam output based on XFEL undulator and electron parameters. This demonstrates the potential of utilizing ANNs for virtual diagnostics linking XFEL electron and photon beam properties.

Would evidence-based regulation improve the practice and management of patient care?

The use of evidence to achieve sound medical diagnoses and optimal treatment plans is considered a standard of practice for healthcare providers. Indeed, failure to do so is prima facie evidence of malpractice. Health and medical care managers have begun espousing a similar philosophy: to make decisions that are data-driven rather than based on logic, intuition, personal preference, or last experience. Unfortunately, regulatory policies and practices in patient care are not always founded upon strong evidence. As a result, unintended consequences often surface after the passage of legislation or the adoption of policies by nongovernmental entities. These dysfunctions might be avoided if policymakers embraced evidence-based protocols commonly found throughout medicine and its management. This paper reviews the dilemmas that unfold when policy is formed without giving sufficient attention, in advance, to "hard" evidence.

Strategic planning to reduce medical errors: Part II--therapy.

In Part I of this series, medical errors were analyzed from a systems dynamics viewpoint. It was noted that despite extensive dialogue and a continuing stream of proposed medical practice revisions, medical errors and adverse impacts persist. Connectivity of vital elements is often underestimated or not fully understood. In Part II, our analysis suggests that the most fruitful strategies for dissolving medical errors include facilitating physician learning, educating patients about appropriate expectations surrounding treatment regimens, and creating "systematic" patient protections rather than depending on (nonexistent) perfect providers.

Strategic planning to reduce medical errors: Part I--diagnosis.

Despite extensive dialogue and a continuing stream of proposed medical practice revisions, medical errors and adverse impacts persist. Connectivity of vital elements is often underestimated or not fully understood. This paper analyzes medical errors from a systems dynamics viewpoint (Part I). Our analysis suggests in Part II that the most fruitful strategies for dissolving medical errors include facilitating physician learning, educating patients about appropriate expectations surrounding treatment regimens, and creating "systematic" patient protections rather than depending on (nonexistent) perfect providers.

Silymarin and hepatoprotection.

OBJECTIVE: To determine the hepatoprotective effect of silymarin with Chang cell cultures. Specifically, to investigate the antioxidant properties of silymarin and its protective function in reducing pro-apoptotic markers. METHODS: Intracellular free radical levels were assessed with dichlorofluorescein (DCF) fluorescence after exposing cells to an oxidative stress of 400 µmol/L H2O2 for 20 min. Levels of cellular ATP and bax expression were examined to evaluate the protective effects of silymarin. RESULTS: Silymarin significantly reduced the DCF fluorescence signal. Cell viability, assessed by the MTT assay, showed that silymarin enhanced the cell growth. Drug treatment was also associated with enhanced ATP levels, and reduced Bax and protein mRNA levels. CONCLUSION: Silymarin can function as a hepatoprotectant against free radical damage due to oxidative stress. The protective nature extends to reducing levels of pro-apoptotic Bax protein. Silymarin may be a useful adjuvant for the treatment of specific liver diseases.

Personalized pharmacotherapy for treatment approaches focused at primary insomnia.

The treatment of primary insomnia may be complex and clinically challenging. A comprehensive multidimensional evaluation with a thorough history and physical examination coupled with appropriate testing/imaging will facilitate development of a working diagnosis. Optimal treatment strategies of challenging cases typically involve interdisciplinary team approaches (including a sleep medicine specialist) providing multimodal approaches to treatment, including nonpharmacologic and pharmacologic strategies. A stepped care approach to treatment may serve as a useful guide for health care providers unfamiliar with sleep disturbance issues. Treatment plans based on sound medical judgment, clinical insight, and a thorough and global understanding of particular patient's comorbid conditions may lead to optimal patient-specific/patient-focused/patient centered personalized care.