Systemic Analgesic Effects of Electroacupuncture in Healthy Individuals: Thermal Threshhold, Acupuncture Sensation Intensity and De-qi on Quantitative Sensory Test.

Background: Electroacupuncture (EA) has been known to exert analgesic effects according to several reports, but studies investigating the analgesic effect of EA using the quantitative sensory test (QST) are rare. Primary Study Objective: To investigate the analgesic effects of electroacupuncture through changes in thermal thresholds measured using the QST. Design: Pilot, randomized, single-blind, parallel design. Setting: The study was conducted at Dongguk University Bundang Oriental Hospital (DUBOH) in South Korea. Participants: We included 40 healthy participants age 20 to 40 years. Intervention: The EA group received EA for 30 minutes at 6 acupuncture points (LI4, PC6, LI10, LI11, ST36, and SP6) and the control group just rested. Outcome measures: The primary outcome measure was 4 thermal thresholds including warm detection (WDT), cold detection (CDT), hot pain (HPT), and cold pain (CPT) measured using QST at baseline and after 15, 30 and 60 minutes. The secondary outcomes were the intensity of acupuncture sensation (visual analogue scale [VAS]) and De-qi (Massachusetts General Hospital Acupuncture Sensation Scale [MASS]). Results: The EA group showed significant changes in HPT (P < .001) and CPT (P = .049) compared with the control group, whereas WDT and CDT did not significantly differ. Furthermore, the changes in thermal thresholds were more pronounced in the higher intensity acupuncture sensation group (VAS ≥40) than in the lower intensity group (VAS < 40), although not significantly. The high De-qi group presented greater changes in WDT, CDT, HPT and CPT than the low De-qi group, as measured using MASS. It was especially statistically significant at HPT a feeling of "heaviness" and "dull pain" and at CDT of "tingling." We observed no adverse events related to the study. Conclusion: The change in thermal pain thresholds effected by EA supports the analgesic effect of EA reported in previous studies. The underlying mechanisms need to be holistically considered, and further studies are needed for definitive evidence.

Treatment of Refractory Low Back Pain Using Passive Recharge Burst in Patients Without Options for Corrective Surgery: Findings and Results From the DISTINCT Study, a Prospective Randomized Multicenter Controlled Trial.

OBJECTIVE: Spinal cord stimulation (SCS) is effective for relieving chronic intractable pain conditions. The Dorsal spInal cord STImulatioN vs mediCal management for the Treatment of low back pain study evaluates the effectiveness of SCS compared with conventional medical management (CMM) in the treatment of chronic low back pain in patients who had not undergone and were not candidates for lumbar spine surgery. METHODS AND MATERIALS: Patients were randomized to passive recharge burst therapy (n = 162) or CMM (n = 107). They reported severe pain and disability for more than a decade and had failed a multitude of therapies. Common diagnoses included degenerative disc disease, spondylosis, stenosis, and scoliosis-yet not to a degree amenable to surgery. The six-month primary end point compared responder rates, defined by a 50% reduction in pain. Hierarchical analyses of seven secondary end points were performed in the following order: composite responder rate (numerical rating scale [NRS] or Oswestry Disability Index [ODI]), NRS, ODI, Pain Catastrophizing Scale responder rate, Patient Global Impression of Change (PGIC) responder rate, and Patient-Reported Outcome Measure Information System-29 in pain interference and physical function. RESULTS: Intention-to-treat analysis showed a significant difference in pain responders on NRS between SCS (72.6%) and CMM (7.1%) arms (p < 0.0001). Of note, 85.2% of those who received six months of therapy responded on NRS compared with 6.2% of those with CMM (p < 0.0001). All secondary end points indicated the superiority of burst therapy over CMM. A composite measure on function or pain relief showed 91% of subjects with SCS improved, compared with 16% of subjects with CMM. A substantial improvement of 30 points was observed on ODI compared with a

Comparison between polynomial regression and weighted least squares regression analysis for verification of analytical measurement range.

OBJECTIVES: Recently, the linearity evaluation protocol by the Clinical & Laboratory Standards Institute (CLSI) has been revised from EP6-A to EP6-ED2, with the statistical method of interpreting linearity evaluation data being changed from polynomial regression to weighted least squares linear regression (WLS). We analyzed and compared the analytical measurement range (AMR) verification results according to the present and prior linearity evaluation guidelines. METHODS: The verification of AMR of clinical chemistry tests was performed using five samples with two replicates in three different laboratories. After analyzing the same evaluation data in each laboratory by the polynomial regression analysis and WLS methods, results were compared to determine whether linearity was verified across the five sample concentrations. In addition, whether the 90% confidence interval of deviation from linearity by WLS was included in the allowable deviation from linearity (ADL) was compared. RESULTS: A linearity of 42.3-56.8% of the chemistry items was verified by polynomial regression analysis in three laboratories. For analysis of the same data by WLS, a linearity of 63.5-78.3% of the test items was verified where the deviation from linearity of all five samples was within the ADL criteria, and the cases where the 90% confidence interval of all deviation from linearity overlapped the ADL was 78.8-91.3%. CONCLUSIONS: Interpreting AMR verification data by the WLS method according to the newly revised CLSI document EP6-ED2 could reduce laboratory workload, enabling efficient laboratory practice.

Surgical decompression for malignant cerebral oedema after ischaemic stroke.

BACKGROUND: Large territory middle cerebral artery (MCA) ischaemic strokes account for around 10% of all ischaemic strokes and have a particularly devastating prognosis when associated with malignant oedema. Progressive cerebral oedema starts developing in the first 24 to 48 hours of stroke ictus with an associated rise in intracranial pressure. The rise in intracranial pressure may eventually overwhelm compensatory mechanisms leading to a cascading secondary damage to surrounding unaffected parenchyma. This downward spiral can rapidly progress to death or severe neurological disability. Early decompressive craniectomy to relieve intracranial pressure and associated tissue shift can help ameliorate this secondary damage and improve outcomes. Evidence has been accumulating of the benefit of early surgical decompression in stroke patients. Earlier studies have excluded people above the age of 60 due to associated poor outcomes; however, newer trials have included this patient subgroup. This review follows a Cochrane Review published in 2012. OBJECTIVES: To assess the effectiveness of surgical decompression in people with malignant oedema after ischaemic stroke with regard to reduction in mortality and improved functional outcome. We also aimed to examine the adverse effects of surgical decompression in this patient cohort. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 7 of 12), MEDLINE Ovid, Embase Ovid, Web of Science Core Collection, Scopus databases, ClinicalTrials.gov, and the WHO ICTRP to July 2022. We also reviewed the reference lists of relevant articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing decompressive craniectomy with medical management to best medical management alone for people with malignant cerebral oedema after MCA ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed study eligibility, performed risk of bias assessment, and extracted the data. The primary outcomes were death and death or severe disability (modified Rankin Scale (mRS) > 4) at 6 to 12 months follow-up. Other outcomes included death or moderate disability (mRS > 3), severe disability (mRS = 5), and adverse events. We assessed the certainty of the evidence using the GRADE approach, categorising it as high, moderate, low, or very low. MAIN RESULTS: We included nine RCTs with a total of 513 participants included in the final analysis. Three studies included patients younger than 60 years of age; two trials accepted patients up to 80 years of age; and one trial only included patients 60 years or older. The majority of included trials (six) mandated a time from stroke ictus to treatment of < 48 hours, whilst in two of them this was < 96 hours. Surgical decompression was associated with a reduction in death (odds ratio (OR) 0.18, 95% confidence interval (CI) 0.12 to 0.27, 9 trials, 513 participants, P < 0.001; high-certainty evidence); death or severe disability (mRS > 4, OR 0.22, 95% CI 0.15 to 0.32, 9 trials, 513 participants, P < 0.001; high-certainty evidence); and death or moderate disability (mRS > 3, OR 0.34, 95% CI 0.22 to 0.52, 9 trials, 513 participants, P < 0.001; moderate-certainty evidence). Subgroup analysis did not reveal any significant effect on treatment outcomes when analysing age (< 60 years versus ≥ 60 years); time from stroke ictus to intervention (< 48 hours versus ≥ 48 hours); or dysphasia. There was a significant subgroup effect of time at follow-up (6 versus 12 months, P = 0.02) on death as well as death or severe disability (mRS > 4); however, the validity of this finding was affected by fewer participant numbers in the six-month follow-up subgroup. There was no consistent reporting of per-participant adverse event rates in any of the included studies, which prevented further analysis. AUTHORS' CONCLUSIONS: Surgical decompression improves outcomes in the management of malignant oedema after acute ischaemic stroke, including a considerable reduction in death or severe disability (mRS > 4) and a reduction in death or moderate disability (mRS > 3). Whilst there is evidence that this positive treatment effect is present in patients > 60 years old, it is important to take into account that these patients have a poorer prospect of functional survival independent of this treatment effect. In interpreting these results it must also be considered that the data demonstrating benefit are drawn from a unique patient subset with profound neurological deficit, reduced level of consciousness, and no pre-morbid disability or severe comorbidity.

Association between physical activity and risk of renal function decline and mortality in community-dwelling older adults: a nationwide population-based cohort study.

BACKGROUND: Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults. METHODS: Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated. RESULTS: Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70-0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53-0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68-0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model. CONCLUSIONS: High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults.

Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is characterised by both metabolic and reproductive disorders, and affects 5% to 15% of women of reproductive age. Different western medicines have been proposed for PCOS-related subfertility, such as oral contraceptives, insulin sensitisers and laparoscopic ovarian drilling (LOD). Chinese herbal medicines (CHM) have also been used for subfertility caused by PCOS for decades, and are expected to become an alternative treatment for subfertile women with PCOS. OBJECTIVES: To assess the efficacy and safety of Chinese herbal medicine (CHM) for subfertile women with polycystic ovarian syndrome (PCOS). SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and six other databases, from inception to 2 June 2020. In addition, we searched three trials registries, the reference lists of included trials and contacted experts in the field to locate trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing CHM versus placebo, no treatment or conventional (western) therapies for the treatment of subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion, assessed the risk of bias in included studies and extracted data. We contacted primary study authors for additional information. We conducted meta-analyses. We used the odds ratios (ORs) to report dichotomous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: We included eight RCTs with 609 participants. The comparisons in the included trials were as follows: CHM versus clomiphene, CHM plus clomiphene versus clomiphene (with or without ethinyloestradiol cyproterone acetate (EE/CPA)), CHM plus follicle aspiration plus ovulation induction versus follicle aspiration plus ovulation induction alone, and CHM plus laparoscopic ovarian drilling (LOD) versus LOD alone. The overall certainty of the evidence for most comparisons was very low. None of the included studies reported the primary outcome, live birth rate. Most studies reported the secondary outcomes, and only one study reported data on adverse events. In trials that compared CHM to clomiphene (with or without LOD in both study arms), we are uncertain of the effect of CHM on pregnancy rates (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.63 to 3.19; I2 = 28%; 3 studies, 140 participants; very low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 21.5%, the chance following CHM would vary between 14.7% and 46.7%. No study reported data on adverse events. When CHM plus clomiphene was compared to clomiphene (with or without EE/CPA), there was low certainty evidence of a higher pregnancy rate in the CHM plus clomiphene group (OR 3.06, 95% CI 2.05 to 4.55; I2 = 10%; 6 studies, 470 participants; low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 31.5%, the chance following CHM plus clomiphene would vary between 48.5% and 67.7%. No data were reported on adverse events. In trials that compared CHM plus follicle aspiration and ovulation induction to follicle aspiration and ovulation induction alone, we are uncertain of the effect of CHM on pregnancy rates (OR 1.62, 95% CI 0.46 to 5.68; 1 study, 44 women; very low certainty evidence). Results suggest that if the chance of pregnancy following follicle aspiration and ovulation induction is assumed to be 29.2%, the chance following CHM with follicle aspiration and ovulation induction would vary between 15.9% and 70%. Reported adverse events included severe luteinised unruptured follicle syndrome (LUFS) (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence), ovarian hyperstimulation syndrome (OHSS) (Peto OR 0.16, 95% CI 0.00 to 8.19; 1 study, 44 women; very low certainty evidence) or multiple pregnancy (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence). These results suggest that if the chances of LUFS, OHSS, and multiple pregnancy following follicle aspiration and ovulation induction are assumed to be 8.3%, 4.2%, and 8.3% respectively, the chances following CHM with follicle aspiration and ovulation induction would be 0.5% to 35.8%, 0% to 26.3% and 0.5% to 35.8% respectively.  In trials that compared CHM plus LOD to LOD alone, we are uncertain if CHM improves pregnancy rates (OR 3.50, 95% CI 0.72 to 17.09; 1 study, 30 women; very low certainty evidence). Results suggest that if the chance of pregnancy following LOD is assumed to be 40%, the chance following CHM with LOD would vary between 32.4% and 91.9%. No data were reported on adverse events. We are uncertain of the results in the comparison groups for all outcomes. The certainty of the evidence for all other comparisons and outcomes was very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail and imprecision due to very low event rates and wide CIs. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of CHM for subfertile women with PCOS. No data are available on live birth. We are uncertain of the effect of CHM on pregnancy rates for there is no consistent evidence to indicate that CHM influences fertility outcomes. However, we find that the addition of CHM to clomiphene may improve pregnancy rates, but there is very limited, low certainty evidence for this outcome. Furthermore, there is insufficient evidence on adverse effects to indicate whether CHM is safe. In the future, well-designed, carefully conducted RCTs are needed, with a particular focus on the live birth rate and other safety indexes.

Abnormal shoot growth in Korean red pine as a response to microclimate changes due to urbanization in Korea.

Impacts of climate change (e.g., abnormal growth in plants, early flowering, and shifting vegetation zones) are being detected throughout the world. Urban land use and its resulting microclimates work in conjunction with the impacts of climate change. Among the principal environmental signals that modulate bud flush, only temperature has changed significantly in recent years. Throughout South Korea, abnormal shoots (usually known as lammas shoots) in Korean red pine (Pinus densiflora), which were once a rare phenomenon, have become notably more common in recent years. The phenomenon is prominent in urban site of each local area. These abnormal shoots appear at a higher frequency and grow to longer lengths in Seoul's hotter urban center than in suburban sites and showed a close positive correlation with urban density and a close negative correlation with vegetation cover expressed as NDVI. Differences in temperature among the urban center, urban edge, and suburban greenbelt were significantly correlated with land-use intensity. Korean red pines planted in urban parks at sites in urban centers showed a lower frequency of abnormal shoots, and the length of the shoots was shorter, compared with those at the other urban sites. Furthermore, the phenology of Korean red pines in an urban park with a fountain showed a spatial difference, depending upon the distance from the fountain: pine trees close to the fountain did not produce abnormal shoots, but abnormal shoot growth increased with the distance from the fountain. These results are noteworthy because they are related to the cooling effects of evapotranspiration from vegetated landscapes and evaporation from a water body. From the results of this study, we could confirm that microclimate change due to urbanization accelerates the impacts of climate change on plant phenology. Furthermore, we identified the possibility that judicious land-use planning could contribute to minimizing the adverse effects of climate change.

Terminal lucidity in the teaching hospital setting.

Terminal lucidity is an unpredictable end-of-life experience that has invaluable implications in preparation for death. We retrospectively evaluated terminal lucidity at a university teaching hospital. Of 338 deaths that occurred during the study period (187 in the ICU and 151 in general wards), terminal lucidity was identified in 6 cases in general wards. Periods of lucidity ranged from several hours to 4 days. After experiencing terminal lucidity, half of the patients died within a week, and the remainder died within 9 days. More attention should be directed toward understanding terminal lucidity to improve end-of-life care in a meaningful way.

Effect of the Contents in Advance Directives on Individuals' Decision-Making.

Completing an advance directive offers individuals the opportunity to make informed choices about end-of-life care. However, these decisions could be influenced in different ways depending on how the information is presented. We randomly presented 185 participants with four distinct types of advance directive: neutrally framed (as reference), negatively framed, religiously framed, and a combination. Participants were asked which interventions they would like to receive at the end of life. Between 60% and 70% of participants responded "accept the special interventions" on the reference form. However, the majority (70%-90%) chose "refuse the interventions" on the negative form. With respect to the religious form, 70% to 80% chose "not decided yet." Participants who refused special life-sustaining treatments were older, female, and with better prior knowledge about advance directives. Our findings imply that the specific content of advance directives could affect decision-making with regard to various interventions for end-of-life care.

Anti-psoriatic effect of myeloid-derived suppressor cells on imiquimod-induced skin inflammation in mice.

Myeloid-derived suppressor cells (MDSCs) play an important role in controlling the immune response against cancer and in suppression of autoimmunity and allergic inflammation. However, the beneficial effects of MDSCs on the experimental mouse model of psoriasis have not been reported. Therefore, we investigated the anti-psoriatic effect of MDSCs on IMQ-induced skin inflammation in mice and explored the mechanisms involved. Our results showed that administration of MDSCs (1 × 106 or 2 × 106  cells) suppressed the development of IMQ-induced skin inflammation in mice as exemplified by a significant reduction in clinical severity scores and was associated with a reduction of histopathological changes, including inflammatory infiltration, epidermal hyperplasia and hyperkeratosis. The immunosuppressive effect of MDSCs (1 × 106 or 2 × 106  cells) corresponded to the production of Th1 cytokines (TNF-α, IFN-γ) and Th17 cytokines (IL-17A and IL-23) in the serum and dorsal skin. Administration of MDSCs (1 × 106 or 2 × 106  cells) also inhibited splenomegaly. Moreover, an increased percentage of CD4+ CD25+ FoxP3+ regulatory T (Treg) cells and decreased percentage of Th1 and Th17 cells were found in mice treated with MDSCs. Taken together, these results imply that MDSCs have immunomodulatory and immunosuppressive effects on disease progression in a murine model of psoriasis and that MDSCs could be used in preventive or therapeutic strategies for the management of autoimmune inflammatory skin disorders, such as psoriasis.

The efficacy of using acupuncture in managing polycystic ovarian syndrome.

PURPOSE OF REVIEW: Polycystic ovarian syndrome (PCOS) is a common reproductive disorder, which significantly impairs the fertility of 3-10% of women at reproductive age. It is getting very popular for women with PCOS to seek alternative therapies to treat PCOS, for example, acupuncture. This review examines the currently available evidence from the randomized controlled trial to guide future recommendation on using acupuncture to assist the treatment of PCOS. RECENT FINDINGS: PCOS is manifested by oligo-amenorrhoea, infertility, and hirsutism. The standard treatment of PCOS includes oral pharmacological agents, lifestyle changes, and surgical modalities. Pharmacologically based therapies are only effective in 60% of the patients, which are also associated with different side-effects. As such, acupuncture offered an alternative option. Acupuncture can affect ß-endorphin production, which may, in turn, affect gonadotropin-releasing hormone secretion and affecting ovulation and menstrual cycle. Therefore, it is postulated that acupuncture may induce ovulation and restore menstrual cycle via increasing ß-endorphin production. SUMMARY: Although modern medical science has discovered the action mechanisms underlying how acupuncture may manage the symptoms of PCOS, majority of the trials are small in sample size and lack of consistency in the choice of acupoints. Larger scale trials are needed to provide standardized protocols.

Acupuncture for polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea, infertility and hirsutism. Conventional treatment of PCOS includes a range of oral pharmacological agents, lifestyle changes and surgical modalities. Beta-endorphin is present in the follicular fluid of both normal and polycystic ovaries. It was demonstrated that the beta-endorphin levels in ovarian follicular fluid of otherwise healthy women who were undergoing ovulation were much higher than the levels measured in plasma. Given that acupuncture impacts on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion, it is postulated that acupuncture may have a role in ovulation induction via increased beta-endorphin production effecting GnRH secretion. This is an update of our previous review published in 2016. OBJECTIVES: To assess the effectiveness and safety of acupuncture treatment for oligo/anovulatory women with polycystic ovarian syndrome (PCOS) for both fertility and symptom control. SEARCH METHODS: We identified relevant studies from databases including the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CNKI, CBM and VIP. We also searched trial registries and reference lists from relevant papers. CENTRAL, MEDLINE, Embase, PsycINFO, CNKI and VIP searches are current to May 2018. CBM database search is to November 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that studied the efficacy of acupuncture treatment for oligo/anovulatory women with PCOS. We excluded quasi- or pseudo-RCTs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, extracted data and assessed risk of bias. We calculated risk ratios (RR), mean difference (MD), standardised mean difference (SMD) and 95% confidence intervals (CIs). Primary outcomes were live birth rate, multiple pregnancy rate and ovulation rate, and secondary outcomes were clinical pregnancy rate, restored regular menstruation period, miscarriage rate and adverse events. We assessed the quality of the evidence using GRADE methods. MAIN RESULTS: We included eight RCTs with 1546 women. Five RCTs were included in our previous review and three new RCTs were added in this update of the review. They compared true acupuncture versus sham acupuncture (three RCTs), true acupuncture versus relaxation (one RCT), true acupuncture versus clomiphene (one RCT), low-frequency electroacupuncture versus physical exercise or no intervention (one RCT) and true acupuncture versus Diane-35 (two RCTs). Studies that compared true acupuncture versus Diane-35 did not measure fertility outcomes as they were focused on symptom control.Seven of the studies were at high risk of bias in at least one domain.For true acupuncture versus sham acupuncture, we could not exclude clinically relevant differences in live birth (RR 0.97, 95% CI 0.76 to 1.24; 1 RCT, 926 women; low-quality evidence); multiple pregnancy rate (RR 0.89, 95% CI 0.33 to 2.45; 1 RCT, 926 women; low-quality evidence); ovulation rate (SMD 0.02, 95% CI -0.15 to 0.19, I2 = 0%; 2 RCTs, 1010 women; low-quality evidence); clinical pregnancy rate (RR 1.03, 95% CI 0.82 to 1.29; I2 = 0%; 3 RCTs, 1117 women; low-quality evidence) and miscarriage rate (RR 1.10, 95% CI 0.77 to 1.56; 1 RCT, 926 women; low-quality evidence).Number of intermenstrual days may have improved in participants receiving true acupuncture compared to sham acupuncture (MD -312.09 days, 95% CI -344.59 to -279.59; 1 RCT, 141 women; low-quality evidence).True acupuncture probably worsens adverse events compared to sham acupuncture (RR 1.16, 95% CI 1.02 to 1.31; I2 = 0%; 3 RCTs, 1230 women; moderate-quality evidence).No studies reported data on live birth rate and multiple pregnancy rate for the other comparisons: physical exercise or no intervention, relaxation and clomiphene. Studies including Diane-35 did not measure fertility outcomes.We were uncertain whether acupuncture improved ovulation rate (measured by ultrasound three months post treatment) compared to relaxation (MD 0.35, 95% CI 0.14 to 0.56; 1 RCT, 28 women; very low-quality evidence) or Diane-35 (RR 1.45, 95% CI 0.87 to 2.42; 1 RCT, 58 women; very low-quality evidence).Overall evidence ranged from very low quality to moderate quality. The main limitations were failure to report important clinical outcomes and very serious imprecision. AUTHORS' CONCLUSIONS: For true acupuncture versus sham acupuncture we cannot exclude clinically relevant differences in live birth rate, multiple pregnancy rate, ovulation rate, clinical pregnancy rate or miscarriage. Number of intermenstrual days may improve in participants receiving true acupuncture compared to sham acupuncture. True acupuncture probably worsens adverse events compared to sham acupuncture.No studies reported data on live birth rate and multiple pregnancy rate for the other comparisons: physical exercise or no intervention, relaxation and clomiphene. Studies including Diane-35 did not measure fertility outcomes as the women in these trials did not seek fertility.We are uncertain whether acupuncture improves ovulation rate (measured by ultrasound three months post treatment) compared to relaxation or Diane-35. The other comparisons did not report on this outcome.Adverse events were recorded in the acupuncture group for the comparisons physical exercise or no intervention, clomiphene and Diane-35. These included dizziness, nausea and subcutaneous haematoma. Evidence was very low quality with very wide CIs and very low event rates.There are only a limited number of RCTs in this area, limiting our ability to determine effectiveness of acupuncture for PCOS.

Alkaloids from Piper nigrum Exhibit Antiinflammatory Activity via Activating the Nrf2/HO-1 Pathway.

In the present study, ten alkaloids, namely chabamide (1), pellitorine (2), retrofractamide A (3), pyrroperine (4), isopiperolein B (5), piperamide C9:1 (8E) (6), 6,7-dehydrobrachyamide B (7), 4,5-dihydropiperine (8), dehydropipernonaline (9), and piperine (10), were isolated from the fruits of Piper nigrum. Among these, chabamide (1), pellitorine (2), retrofractamide A (3), isopiperolein B (5), and 6,7-dehydrobrachyamide B (7) exhibited significant inhibitory activity on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, with IC50 values of 6.8, 14.5, 30.2, 23.7, and 38.5 µM, respectively. Furthermore, compound 1 inhibited lipopolysaccharide-induced NO production in bone marrow-derived macrophages with IC50 value of 9.5 µM. Consistent with NO inhibition, treatment of RAW264.7 cells with chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) suppressed expression of inducible NO synthase and cyclooxygenase-2. Chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) induced heme-oxygenase-1 expression at the transcriptional level. In addition, compound 1 induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and upregulated the expression of Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 and γ-glutamyl cysteine synthetase catalytic subunit, in a concentration-dependent manner in RAW264.7 cells. These findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme-oxygenase-1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases. Copyright © 2017 John Wiley & Sons, Ltd.

Long-term outcomes of ethanol injection therapy for locally recurrent papillary thyroid cancer.

The standard treatment regimen for locally recurrent lesions is total thyroidectomy, or complete removal of the recurrent thyroid lesion within the thyroid bed. However, reoperation increases the risk of complications and patients have to undergo general anesthesia. Percutaneous ethanol injection therapy represents a far less invasive procedure without general anesthesia and with lower risk of complications. Thirty-four patients who received PEIT at Yonsei University Medical Center between October 2002 and August 2009 for recurrent cervical nodal metastases of differentiated papillary thyroid cancer were included in this retrospective study. During a minimum follow-up of 60 months, treatment outcomes were determined by measuring the lesion size prior to the first injection and 3 months after the last injection. A total of 46 recurrent lesions were detected in 34 patients. Five patients underwent surgery and PEIT was administered to the remaining 19 and 22 lesions in the central compartment and lateral neck lymph nodes, respectively. Size increases were observed in seven (17.1%) lesions, whereas no changes in size and decreases were detected in 10 (24.4%) and 24 (58.5%) lesions. Patients with increased lymph nodes were significantly older (65.3 ± 14.4 vs. 48.2 ± 16.3 years; p = 0.02) and had smaller sizes (9.3 ± 1.0 vs. 12.3 ± 6.4 mm; p = 0.012). Although reoperation remains the first-line treatment for recurrent thyroid cancer, PEIT may be considered as a treatment option in selected patients with lesions larger than 1 cm who are ineligible for surgery or have refused reoperation.

Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrinology abnormalities, and affects 5% to 10% of women of reproductive age. Western medicines, such as oral contraceptives, insulin sensitizers and laparoscopic ovarian drilling (LOD), have been used to treat PCOS. Recently, many studies have been published that consider Chinese herbal medicine (CHM) as an alternative treatment for women with PCOS. OBJECTIVES: To assess the efficacy and safety of CHM for subfertile women with PCOS. SEARCH METHODS: We searched sources, including the following databases, from inception to 9 June 2016: the Cochrane Gynaecology and Fertility Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Allied and Complementary Medicine (AMED), PsycINFO, Chinese National Knowledge Infrastructure (CNKI), VIP, Wanfang and trial registries. In addition, we searched the reference lists of included trials and contacted experts in the field to locate trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) that considered the use of CHM for the treatment of subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Two review authors independently screened appropriate trials for inclusion, assessed the risk of bias in included studies and extracted data. We contacted primary study authors for additional information. We conducted meta-analyses. We used the odds ratios (ORs) to report dichotomous data, with 95% confidence intervals (CI). We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: We included five RCTs with 414 participants. The comparisons in the included trials were as follows: CHM versus clomiphene, CHM plus clomiphene versus clomiphene (with or without ethinyloestradiol cyproterone acetate (CEA)), CHM plus follicle aspiration plus ovulation induction versus follicle aspiration plus ovulation induction alone, and CHM plus laparoscopic ovarian drilling (LOD) versus LOD alone. The overall quality of the evidence for most comparisons was very low.None of the included studies reported live birth rate, and only one study reported data on adverse events.When CHM was compared with clomiphene (with or without LOD in both arms), there was no evidence of a difference between the groups in pregnancy rates (odds ratio (OR) 1.98, 95% confidence interval (CI) 0.78 to 5.06; two studies, 90 participants, I² statistic = 0%, very low quality evidence). No study reported data on adverse events. When CHM plus clomiphene was compared with clomiphene (with or without CEA), there was low quality evidence of a higher pregnancy rate in the CHM plus clomiphene group (OR 2.62, 95% CI 1.65 to 4.14; three RCTs, 300 women, I² statistic = 0%,low quality evidence). No data were reported on adverse events.When CHM with follicle aspiration and ovulation induction was compared with follicle aspiration and ovulation induction alone, there was no evidence of a difference between the groups in pregnancy rates (OR 1.60, 95% CI 0.46 to 5.52; one study, 44 women, very low quality evidence), severe luteinized unruptured follicle syndrome (LUFS) (OR 0.60, 95% CI 0.06 to 6.14; one study, 44 women, very low quality evidence), ovarian hyperstimulation syndrome (OHSS) (OR 0.16, 95% CI 0.00 to 8.19; one study, 44 women, very low quality evidence) or multiple pregnancy (OR 0.60, 95% CI 0.06 to 6.14; one study, 44 women, very low quality evidence).When CHM with LOD was compared with LOD alone, there was no evidence of a difference between the groups in rates of pregnancy (OR 3.50, 95% CI 0.72 to 17.09; one study, 30 women, very low quality evidence), No data were reported on adverse events.There was no evidence of a difference between any of the comparison groups for any other outcomes. The quality of the evidence for all other comparisons and outcomes was very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail and imprecision due to very low event rates and wide CIs. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of CHM for women with PCOS and subfertility. No data are available on live birth, and there is no consistent evidence to indicate that CHM influences fertility outcomes. However there is very limited low quality evidence to suggest that the addition of CHM to clomiphene may improve pregnancy rates. There is insufficient evidence on adverse effects to indicate whether CHM is safe.

Advance care planning for haemodialysis patients.

BACKGROUND: End-stage kidney disease (ESKD) is a chronic, debilitative and progressive illness that may need interventions such as dialysis, transplantation, dietary and fluid restrictions. Most patients with ESKD will require renal replacement therapy, such as kidney transplantation or maintenance dialysis. Advance care planning traditionally encompass instructions via living wills, and concern patient preferences about interventions such as cardiopulmonary resuscitation and feeding tubes, or circumstances around assigning surrogate decision makers. Most people undergoing haemodialysis are not aware of advance care planning and few patients formalise their wishes as advance directives and of those who do, many do not discuss their decisions with a physician. Advance care planning involves planning for future healthcare decisions and preferences of the patient in advance while comprehension is intact. It is an essential part of good palliative care that likely improves the lives and deaths of haemodialysis patients. OBJECTIVES: The objective of this review was to determine whether advance care planning in haemodialysis patients, compared with no or less structured forms of advance care planning, can result in fewer hospital admissions or less use of treatments with life-prolonging or curative intent, and if patient's wishes were followed at end-of-life. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 27 June 2016 through contact with the Information Specialist using search terms relevant to this review. We also searched the Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Social Work Abstracts (OvidSP). SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at advance care planning versus no form of advance care planning in haemodialysis patients was considered for inclusion without language restriction. DATA COLLECTION AND ANALYSIS: Data extraction was carried out independently by two authors using standard data extraction forms. Studies reported in non-English language journals were translated before assessment. Where more than one publication of one study exists, reports were grouped together and the publication with the most complete data was used in the analyses. Where relevant outcomes are only published in earlier versions these data were used. Any discrepancies between published versions were highlighted. Non-randomised controlled studies were excluded. MAIN RESULTS: We included two studies (three reports) that involved 337 participants which investigated advance care planning for people with ESKD. Neither of the included studies reported outcomes relevant to this review. Study quality was assessed as suboptimal. AUTHORS' CONCLUSIONS: We found sparse data that were assessed at suboptimal quality and therefore we were unable to formulate conclusions about whether advance care planning can influence numbers of hospital admissions and treatment required by people with ESKD, or if patients' advance care directives were followed at end-of-life. Further well designed and adequately powered RCTs are needed to better inform patient and clinical decision-making about advance care planning and advance directives among people with ESKD who are undergoing dialysis.

Acupuncture for polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea, infertility and hirsutism. Conventional treatment of PCOS includes a range of oral pharmacological agents, lifestyle changes and surgical modalities. Beta-endorphin presents in the follicular fluid of both normal and polycystic ovaries. It was demonstrated that the beta-endorphin levels in ovarian follicular fluid of otherwise healthy women who were undergoing ovulation were much higher than the levels measured in plasma. Given that acupuncture has an impact on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion, it is postulated that acupuncture may have a role in ovulation induction and fertility. OBJECTIVES: To assess the effectiveness and safety of acupuncture treatment of oligo/anovulatory women with polycystic ovarian syndrome (PCOS). SEARCH METHODS: We identified relevant studies from databases including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, EMBASE, PsycINFO, CNKI and trial registries. The data are current to 19 October 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that studied the efficacy of acupuncture treatment for oligo/anovulatory women with PCOS. We excluded quasi- or pseudo-RCTs. Primary outcomes were live birth and ovulation (primary outcomes), and secondary outcomes were clinical pregnancy, restoration of menstruation, multiple pregnancy, miscarriage and adverse events. We assessed the quality of the evidence using GRADE methods. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, extracted data and assessed risk of bias. We calculated Mantel-Haenszel odds ratios (ORs) and mean difference (MD) and 95% confidence intervals (CIs). MAIN RESULTS: We included five RCTs with 413 women. They compared true acupuncture versus sham acupuncture (two RCTs), true acupuncture versus relaxation (one RCT), true acupuncture versus clomiphene (one RCT) and electroacupuncture versus physical exercise (one RCT). Four of the studies were at high risk of bias in at least one domain.No study reported live birth rate. Two studies reported clinical pregnancy and found no evidence of a difference between true acupuncture and sham acupuncture (OR 2.72, 95% CI 0.69 to 10.77, two RCTs, 191 women, very low quality evidence).Three studies reported ovulation. One RCT reported number of women who had three ovulations during three months of treatment but not ovulation rate. One RCT found no evidence of a difference in mean ovulation rate between true and sham acupuncture (MD -0.03, 95% CI -0.14 to 0.08, one RCT, 84 women, very low quality evidence). However, one other RCT reported very low quality evidence to suggest that true acupuncture might be associated with higher ovulation frequency than relaxation (MD 0.35, 95% CI 0.14 to 0.56, one RCT, 28 women).Two studies reported menstrual frequency. One RCT reported true acupuncture reduced days between menstruation more than sham acupuncture (MD 220.35, 95% CI 252.85 to 187.85, 146 women). One RCT reported electroacupuncture increased menstrual frequency more than no intervention (0.37, 95% CI 0.21 to 0.53, 31 women).There was no evidence of a difference between the groups in adverse events. Evidence was very low quality with very wide CIs and very low event rates.Overall evidence was low or very low quality. The main limitations were failure to report important clinical outcomes and very serious imprecision. AUTHORS' CONCLUSIONS: Thus far, only a limited number of RCTs have been reported. At present, there is insufficient evidence to support the use of acupuncture for treatment of ovulation disorders in women with PCOS.

The effect of Vaccinium uliginosum extract on tablet computer-induced asthenopia: randomized placebo-controlled study.

BACKGROUND: To investigate the alleviation effect of Vaccinium uliginosum extract (DA9301) on tablet computer-induced asthenopia. METHODS: This was a randomized, placebo-controlled, double-blind and parallel study (Trial registration number: 2013-95). A total 60 volunteers were randomized into DA9301 (n = 30) and control (n = 30) groups. The DA9301 group received DA9301 oral pill (1000 mg/day) for 4 weeks and the control group received placebo. Asthenopia was evaluated by administering a questionnaire containing 10 questions (responses were scored on a scales of 0-6; total score: 60) regarding ocular symptoms before (baseline) and 4 weeks after receiving pills (DA9301 or placebo). The participants completed the questionnaire before and after tablet computer (iPad Air, Apple Inc.) watching at each visit. The change in total asthenopia score (TAS) was calculated and compared between the groups RESULTS: TAS increased significantly after tablet computer watching at baseline in DA9301 group. (from 20.35 to 23.88; p = 0.031) However, after receiving DA9301 for 4 weeks, TAS remained stable after tablet computer watching. In the control group, TAS changes induced by tablet computer watching were not significant both at baseline and at 4 weeks after receiving placebo. Further analysis revealed the scores for "tired eyes" (p = 0.001), "sore/aching eyes" (p = 0.038), "irritated eyes" (p = 0.010), "watery eyes" (p = 0.005), "dry eyes" (p = 0.003), "eye strain" (p = 0.006), "blurred vision" (p = 0.034), and "visual discomfort" (p = 0.018) significantly improved in the DA9301 group. CONCLUSIONS: We found that oral intake of DA9301 (1000 mg/day for 4 weeks) was effective in alleviating asthenopia symptoms induced by tablet computer watching. TRIAL REGISTRATION: The study is registered at www.clinicaltrials.gov (registration number: NCT02641470, date of registration December 30, 2015).

Clinical Experience With n-Butyl-2-Cyanoacrylate in Performing Lateral Neck Dissection for Metastatic Thyroid Cancer.

Background Chyle leakage following lateral neck dissection (LND) is rare, but can induce metabolic disturbances, delay wound healing, and prolong hospitalization. n-Butyl-2-cyanoacrylate (NBCA) has been used to achieve hemostasis and seal tissues in several surgical settings. We here assessed whether application of NBCA to the thoracic duct area is effective in sealing chyle leakage. Methods The medical records of 163 patients who underwent total thyroidectomy with unilateral LND between March 2011 and September 2012 were reviewed. NBCA was applied to 84 patients and not applied to 79. Drainage volume, duration of hospital stay, and incidence of complications were compared between the 2 groups. Results The 2 groups were not different with regard to age, body weight, gender, primary tumor histology, and number of lateral neck nodes harvested. Mean hospital stay was significantly shorter (4.3 ± 1.8 vs 5.7 ± 3.0 days, P < .001), median total drainage volume was significantly smaller (270 mL; range: 97-931 mL vs 328 mL; range: 113-2636 mL; P < .001), and rate of chyle leakage was significantly lower (0% vs 6.3%, P = .025) in the NBCA than in the non-NBCA group. Conclusion NBCA application to the dissected area of the thoracic duct posterior to its angle of junction with the internal jugular and subclavian veins could be safe and effective in reducing surgical complications related to chyle leakage after LND.