The following represent additions to UpToDate since the last version considered by the authors and editors to be of particular interest.
ANESTHESIA
Exercise testing to diagnose long QT syndrome — A prolonged corrected QT interval (QTc) on a resting electrocardiogram has limited sensitivity for the detection of long QT syndrome. A multicenter study found that a prolonged QTc during exercise recovery provided greater sensitivity [1]. A screening algorithm based upon resting and exercise-recovery QTc performed well in derivation and validation cohorts. (See "Diagnosis of congenital long QT syndrome", section on 'Exercise-recovery QTc'.)
Cardiopulmonary exercise testing — Prognostication is a major challenge in the management of patients with heart failure. More sophisticated cardiopulmonary exercise testing parameters (eg, the oxygen update efficiency plateau [2]) may offer greater prognostic value than currently used measures, but require further validation. (See "Predictors of survival in heart failure due to systolic dysfunction", section on 'Exercise variables'.)
Bridging therapy with cangrelor before CABG — The decision when to discontinue platelet P2Y12 receptor blocker therapy prior to coronary artery bypass graft surgery (CABG) must balance the perioperative risks of bleeding if antiplatelet therapy is continued and acute ischemic events if it is discontinued. The randomized BRIDGE trial evaluated the possible role of bridging therapy (after discontinuation of the oral P2Y12 receptor blocker) using the intravenous agent cangrelor. Cangrelor provided the expected continuous antiplatelet effect and did not increase the rate of CABG related bleeding, but ischemic outcomes were not evaluated and thus the role of bridging therapy has not been established [3]. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Stopping and restarting P2Y12 receptor blocker'.)
Optimal transfusion level — The "optimal" transfusion level for postoperative patients with cardiovascular disease or risk factors was examined in the FOCUS trial [4]. Patients ≥50 years of age with a hemoglobin (Hb) concentration <10 g/dL within three days after hip surgery were randomly assigned to liberal (transfuse to raise Hb to >10 g/dL) or restrictive (transfuse only for symptoms or Hb <8 g/dL) treatment groups. The primary outcome (death or inability to walk a distance unassisted at 60 days) was similar for both groups, suggesting that it is reasonable to withhold transfusion in asymptomatic postoperative patients whose hemoglobin is >8 g/dL, even if they are older and have cardiovascular disease or risk factors. (See "Indications for red cell transfusion in the adult", section on 'Optimal transfusion level'.)
Adherence with continuous positive airway pressure — One night without continuous positive airway pressure (CPAP) is enough to mitigate the benefits of CPAP therapy in patients with obstructive sleep apnea (OSA). The sensitivity of patients to discontinuation of CPAP was illustrated by a trial that included 41 patients with OSA who had been using CPAP successfully for at least one year [5]. After only four nights without CPAP, the frequency of oxyhemoglobin desaturation events increased during sleep, indicating recurrence of OSA. The patients were then randomly assigned to a CPAP withdrawal group (ie, subtherapeutic CPAP) or a CPAP group (ie, therapeutic CPAP) for two weeks. CPAP withdrawal led to recurrence of abnormal respiratory events within one night, increased morning and evening blood pressure within two weeks, and increased morning heart rate within two weeks. Subjective daytime sleepiness also increased within two weeks. CPAP withdrawal was not associated with deterioration of psychomotor performance. (See "Adherence with continuous positive airway pressure (CPAP)", section on 'Consequences'.)
BREAST SURGERY
Radiation therapy after breast conserving surgery — Radiation therapy (RT) is a standard component of the treatment of women who undergo breast conserving surgery (BCS) for breast cancer. The latest meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group confirmed long-lasting benefits of adjuvant RT after BCS [6]. Compared with BCS alone, the addition of RT after BCS was associated with reductions in the 10-year risk of recurrence and in the 15-year risk of breast cancer death. The benefits were consistently seen in both women with node-positive and node-negative breast cancer at diagnosis. (See "Role of radiation therapy in breast conservation therapy", section on 'Benefits'.)
Dual HER2-directed antibody therapy for metastatic breast cancer — HER2 is an important prognostic and predictive factor in breast cancer and the use of the HER2 monoclonal antibody is part of the standard treatment for women with HER2-positive breast cancer. Like trastuzumab, pertuzumab also binds the HER2 receptor but at a different sub-domain. A phase III trial enrolled women with untreated HER2-positive metastatic breast cancer and assigned them to therapy with standard treatment (trastuzumab plus docetaxel) with randomization to include pertuzumab or placebo [7]. Compared with placebo, combining standard treatment with pertuzumab improved the overall response rate and progression-free survival, with a trend towards improved overall survival. While pertuzumab is not approved for use in the United States, this data supports its use as a first-line treatment for women with HER2-positive breast cancer. (See "Systemic treatment for metastatic breast cancer: Biologic therapy", section on 'Pertuzumab'.)
COLORECTAL SURGERY
Sodium phosphate for flexible sigmoidoscopy — The preparation for flexible sigmoidoscopy typically involves two sodium phosphate enemas given the morning of the examination. However, sodium phosphate enemas have been associated with complications, particularly in older adults. A retrospective series found that sodium phosphate enema use in older adults (mean age 80 years, range 61 to 89 years) was associated with complications, including hypotension and volume depletion, hyperphosphatemia, hypo- or hyperkalemia, metabolic acidosis, severe hypocalcemia, renal failure, and changes on the electrocardiogram (prolonged QT interval) [8]. As a result, in patients over the age of 70 years, the risks of oral preparations (eg, polyethylene glycol lavage or magnesium citrate) and sodium phosphate enemas need to be weighed for each individual patient before deciding upon an appropriate preparation. (See "Bowel preparation for flexible sigmoidoscopy and colonoscopy", section on 'Preparation for flexible sigmoidoscopy'.)
Vitamin D and colon cancer — The relationship between vitamin D deficiency and risk of cancer is controversial. In a meta-analysis of nine case-control studies, there was a link between poor vitamin D status and risk of colon cancer [9]. For each 4 ng/mL (10 nmol/L) increase in prediagnosis serum 25OHD concentration, there was a 6 percent reduction in colorectal cancer. (See "Vitamin D and extraskeletal health", section on 'Cancer'.)
Human papilloma virus vaccine for prevention of anal intraepithelial neoplasia — A quadrivalent vaccine has been shown to be effective in preventing infection with human papilloma virus vaccine (HPV) types 6, 11, 16, and 18 and to prevent the development of external genital lesions [10]. A planned substudy of that trial analyzed the impact of the vaccine on the development of anal intraepithelial neoplasia in 602 men who have sex with men [11]. Study subjects were aged 16 to 26 years, had no history or evidence of anal lesions, had five or fewer lifetime sexual partners, and were HIV negative. Administration of the HPV vaccine was associated with a significant decrease in the incidence of anal intraepithelial neoplasia. (See "Anal intraepithelial neoplasia: Diagnosis, screening, prevention, and treatment", section on 'Prevention'.)
Aspirin for chemoprevention in patients with Lynch syndrome — Individuals with Lynch syndrome have an 80 percent risk of developing colorectal cancer in their lifetime. While an earlier placebo-controlled trial (CAPP2) did not find a benefit for aspirin for adenoma or colon cancer prevention in patients with Lynch syndrome after a mean of 29 months of follow-up, a subsequent analysis found a marginally significant reduction in colorectal cancer incidence in the subset of patients treated with 600 mg aspirin per day for more than two years [12]. A secondary analysis found a decreased rate of overall Lynch cancers in the aspirin-treated group. Further studies are needed to validate this potentially important result and determine if the benefits associated with aspirin outweigh the risks. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and management of patients and families", section on 'Chemoprevention' and "NSAIDs (including aspirin): Role in prevention of colorectal cancer", section on 'Aspirin trials'.)
ESOPHAGEAL SURGERY
Risk of esophageal cancer — A 2010 meta-analysis estimated the incidence of esophageal adenocarcinoma in patients with Barrett’s esophagus to be 6.3 cases per 1000 person-years [13]. However, a subsequent large study using the Danish Cancer Registry reported a rate of 1.2 cases per 1000 person-years [14]. This more recent study suggests that the risk of esophageal adenocarcinoma in patients with Barrett's esophagus may be lower than previously suggested. (See "Management of Barrett's esophagus", section on 'Influence of Barrett's esophagus on mortality'.)
GENERAL SURGICAL PRINCIPLES
Fluoroquinolones and retinal detachment — A nested case-control study of patients who had visited an ophthalmologist found an increased rate of retinal detachment in patients who were currently receiving an oral fluoroquinolone [15]. Past fluoroquinolone use (even if recent) was not associated with retinal detachment, suggesting that retinal detachment may be an acute adverse effect. A possible reason for the increased risk of retinal detachment in patients taking a fluoroquinolone is the destructive effect of this class of agents on collagen and connective tissue. This adverse effect requires confirmation in an additional study. (See "Fluoroquinolones", section on 'Retinal detachment'.)
Maneuvers to displace trapped carbon dioxide after laparoscopy — Trapped CO2 gas used in laparoscopy may cause abdominal or shoulder pain after surgery. A trial to assess the most effective strategy for displacing the gas randomly assigned women undergoing gynecologic laparoscopic surgery to one of three arms: instillation of normal saline after release of the pneumoperitoneum, pulmonary maneuvers in which the anesthesiologist manually inflates the thorax to increase intra-abdominal pressure, or no maneuvers (control) [16]. The incidence of postoperative shoulder pain was significantly lower in the saline group 24 hours after surgery and upper abdominal pain was improved for both treatment groups compared with the control group. (See "Abdominal access techniques used in laparoscopic surgery", section on 'Access-related pain'.)
C. difficile and proton pump inhibitors — Proton pump inhibitors (PPIs) may be associated with an increased risk of C. difficile-associated diarrhea (CDAD). The US Food and Drug Administration (FDA) issued a drug safety communication in February 2012 following a review of published literature [17]. Most studies reviewed found that the risk of C. difficile infection or disease, including CDAD, ranged from 1.4 to 2.75 times higher among patients with PPI exposure compared with those without PPI exposure. The relationship between the risk of C. difficile infection and PPI dose and duration of use is uncertain. Given the potential risk of CDAD, the FDA has also recommended that providers prescribe the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. (See "Epidemiology, microbiology, and pathophysiology of Clostridium difficile infection in adults", section on 'Gastric acid suppression' and "Overview and comparison of the proton pump inhibitors for the treatment of acid-related disorders", section on 'Clostridium difficile and other enteric infections'.)
Prevention of pressure ulcers — Based upon cost modeling, several studies have found the use of pressure redistribution surfaces in the hospital to be cost-effective. A cost analysis of preventive strategies used in long-term nursing home care also found that support surfaces are cost effective [18]. In this study, multiple strategies were evaluated including pressure redistribution surfaces, oral nutritional supplements for high-risk residents with recent weight loss, skin emollients for high-risk residents with dry skin, and skin cleansing for high-risk residents requiring incontinence care. Preventive strategies cost, on average, $11.66 per resident per week. The lifetime risk of developing a pressure ulcer was reduced with the use of preventive strategies and the number needed-to-treat to prevent pressure ulcers was calculated to be 45 for pressure redistribution surfaces, 63 for skin cleansing, 158 for skin emollients, and 333 for nutritional supplementation. (See "Prevention of pressure ulcers".)
Risk factors and in-hospital mortality in MI patients — In a study of over 500,000 patients with first myocardial infarction (MI) and no prior cardiovascular disease, there was an inverse relationship between the number of cardiovascular disease risk factors and in-hospital mortality [19]. The explanation for this surprising finding is unknown. (See "Risk factors for adverse outcomes after unstable angina or non-ST elevation myocardial infarction", section on 'Number of CHD risk factors'.)
Bedside assessment of filling pressures — Accurate estimation of cardiac filling pressures is essential to the diagnosis and management of heart failure. A study of patients undergoing catheterization found that physical examination was moderately accurate in estimating right and left heart filling pressures [20]. The accuracy of bedside assessment was greater for staff cardiologists than for trainees. Exposure to the results of noninvasive cardiac testing did not improve the accuracy of estimates of filling pressures. (See "Evaluation of the patient with suspected heart failure", section on 'Diagnostic accuracy of clinical features'.)
Saddle pulmonary embolism — A saddle pulmonary embolism (PE) is a PE that has lodged at the bifurcation of the main pulmonary artery. The hemodynamic consequences of saddle PE and their response to therapy are similar to other types of acute PE. This was demonstrated by a retrospective study of 680 patients with PE, which included 37 patients with saddle PE [21]. Among the patients with saddle PE, transient hypotension occurred in 14 percent, persistent shock occurred in 8 percent, and in-hospital mortality occurred in 5 percent. (See "Overview of acute pulmonary embolism", section on 'Definitions'.)
Parenteral nutrition as an adjunct to enteral nutrition — The use of parenteral nutrition as an adjunct to enteral nutrition to improve provision of calories and protein may be harmful according to two studies. The first study was a multicenter trial that randomly assigned 4640 critically ill adults who were already receiving enteral nutrition to have supplemental parenteral nutrition initiated early (within 48 hours of ICU admission) or late (after the eighth day of ICU admission) [22]. Those who received early parenteral nutrition were more likely to develop a new infection and had a longer duration of mechanical ventilation, ICU stay, and hospitalization. The second study was an observational study that compared three groups: enteral nutrition alone, enteral nutrition plus early parenteral nutrition, and enteral nutrition plus late parenteral nutrition [23]. Enteral nutrition plus either early or late parenteral nutrition was associated with increased mortality compared with enteral nutrition alone. (See "Nutrition support in critically ill patients: An overview", section on 'Parenteral nutrition'.)
Risk stratification for upper gastrointestinal bleeding — The use of risk stratification tools for patients with acute upper gastrointestinal bleeding is recommended by the International Consensus Upper Gastrointestinal Bleeding Conference Group. A new scoring system derived using a large database found that an easily calculated score based upon the patient's albumin, INR, mental status, systolic blood pressure, and age (AIMS65) had a high accuracy for predicting inpatient mortality [24]. The use of the AIMS65 score may be a useful addition to other scoring systems for predicting mortality in patients with acute upper gastrointestinal bleeding. (See "Approach to acute upper gastrointestinal bleeding in adults", section on 'Risk scores'.)
Treatment of angiodysplasia with thalidomide — Inhibitors of angiogenesis, such as thalidomide, may play a role in the treatment of angiodysplasia of the gastrointestinal tract. A randomized trial compared the use of thalidomide with control therapy (oral iron) in patients with recurrent or refractory bleeding from angiodysplasia [25]. The primary end point (decrease in bleeding episodes by at least 50 percent) was found more frequently in patients in the thalidomide group, who also experienced higher rates of cessation of bleeding and independence from transfusion. Thalidomide appears to be a reasonable treatment for patients with recurrent or refractory bleeding from gastrointestinal angiodysplasia who have failed to respond to other therapies. However, due to its teratogenic effects, thalidomide must not be used in women of child bearing potential who are unable to use two reliable forms of birth control for at least one month prior to starting thalidomide and for one month after stopping it. (See "Angiodysplasia of the gastrointestinal tract".)
Malignancy following solid organ transplantation — An increased risk of a wide range of cancers is associated with solid organ transplantation, with specific cancer risk varying with the organ transplanted. A cohort study analyzed the frequency of malignancy in over 175,000 solid organ transplant recipients [26]. The standardized incidence ratio for developing cancer was 2.1 compared with the general population, with an excess absolute risk of 719 cases per 100,000 person-years. The biggest relative increases were seen for Kaposi sarcoma, nonmelanoma skin cancer, non-Hodgkin lymphoma, and cancers of the liver, anus, vulva, and lip. Lung cancer, kidney cancer, colorectal cancer, pancreatic cancer, Hodgkin lymphoma, and melanoma also contributed significantly to the excess risk. (See "Development of malignancy following solid organ transplantation", section on 'General epidemiology'.)
HEPATOBILIARY SURGERY
Prevention of portal vein thrombosis — Preliminary results are available from a prospective, randomized trial of enoxaparin for the prevention of portal vein thrombosis (PVT) in patients with cirrhosis [27]. During the one-year study period, PVT occurred significantly more often in those taking placebo (6 of 36, 17 percent) than in those taking enoxaparin (0 of 34). No hemorrhagic events were attributed to enoxaparin. Enoxaparin use was also associated with a significantly lower incidence of hepatic decompensation (53 versus 12 percent). (See "Coagulation abnormalities in patients with liver disease", section on 'Prevention'.)
Osteoporosis following liver transplantation — A meta-analysis of nine trials evaluating the effect of treatment with bisphosphonates versus control (placebo or no treatment) on fracture outcomes after solid organ (liver, heart, kidney) transplantation showed a reduction in the proportion of patients with fracture after treatment with bisphosphonates [28]. (See "Osteoporosis after solid organ or stem cell transplantation", section on 'Bisphosphonates'.)
UROLOGIC SURGERY
Use of stents in conjunction with ureteroscopy — Stents are often placed after ureteroscopy lithotripsy in an effort to prevent obstruction and pain. A meta-analysis of 16 randomized trials involving 1573 patients evaluated the benefits of stent placement after ureteroscopy [29]. Compared with those who did not receive a stent, patients receiving stents had significantly longer operative times, and more pain and lower urinary tract symptoms (dysuria, frequency or urgency, and hematuria), while there was no difference in stone free rate, fever, urinary tract infection, requirement for analgesia, urinary strictures, or unplanned rehospitalization. Thus, routine placement of stents after uncomplicated ureteroscopy should be discouraged. (See "Options in the management of renal and ureteral stones in adults", section on 'Indications for stent placement'.)
Anticholinergic medication for overactive bladder symptoms — A systematic review of 86 randomized trials and meta-analysis of 70 trials in patients with overactive bladder symptoms compared differing doses and formulations of four anticholinergic drugs [30]. Tolterodine was better tolerated than oxybutynin, though efficacy was similar for both, and extended-release formulations of these agents were better tolerated than immediate release. Fesoterodine had better efficacy than extended-release tolterodine but caused more dry mouth leading to drug withdrawal. Solifenacin was more effective and better tolerated than immediate-release tolterodine. Data were not available for other comparisons and data did not allow conclusions about comparative costs, long-term outcomes, or the impact on quality of life. (See "Treatment of urinary incontinence", section on 'Antimuscarinics'.)
Calcineurin inhibitors and renal allograft failure — A meta-analysis that included 17 studies (4131 patients) showed that calcineurin inhibitor-minimizing regimens were associated with reduced overall graft failure and death-censored graft failure with no difference in graft failure secondary to rejection [31]. (See "Chronic renal allograft nephropathy", section on 'Changes in calcineurin inhibitor exposure'.)
ACOG and AUGS recommendations regarding transvaginal mesh for pelvic organ prolapse repair — The American College of Obstetricians and Gynecologists and the American Urogynecologic Society issued a joint statement in response to the US Food and Drug Administration warning (September, 2011) regarding use of transvaginal mesh for pelvic organ prolapse repair [32]. The recommendations included: limiting vaginal mesh repair to women for whom the benefit of mesh use outweighs the risks (eg, recurrent prolapse or comorbidities precluding more invasive procedures), device-specific training for surgeons, and reporting of outcome data for transvaginal mesh procedures. (See "Reconstructive materials in urogynecology: Clinical applications".)
SOFT TISSUE AND PLASTIC SURGERY
Risk of skin cancer — Data on the risk of nonmelanoma skin cancer (NMSC) in thiopurine exposed IBD patients have been conflicting. In a nested case-control analysis of a large historical cohort study, the use of thiopurines was associated with a significant increase in the risk of squamous cell skin cancer [33]. In another cohort study, both ongoing and past exposure to thiopurines was associated with a significant increase in the risk of NMSC in patients with IBD [34]. These results suggest that patients with IBD on thiopurines may benefit from protection against UV radiation and dermatologic screening. (See "Skin and eye manifestations of inflammatory bowel disease", section on 'Miscellaneous skin lesions'.)
MINIMALLY INVASIVE SURGERY
Bipolar sealing devices for vaginal hysterectomy — Bipolar vessel sealing devices may be used as an alternative to suturing for ligation of the uterine vessels during vaginal hysterectomy. A meta-analysis of seven randomized trials of women undergoing vaginal hysterectomy found that use of energy-based vessel sealing devices (eg, LigaSure™, BiClamp®) decreased blood loss by an average of 48 mL and operative duration by an average of 17 minutes compared with suturing [35]. (See "Vaginal hysterectomy", section on 'Ligating the uterine vessels'.)
THORACIC SURGERY
Screening for lung cancer — The National Comprehensive Cancer Network (NCCN) issued guidelines for lung cancer screening in October 2011 [36]. These guidelines recommend annual low-dose CT scan screening for those at high risk and no routine screening for moderate- or low-risk individuals. High risk was defined as age 55 to 74 years with a 30 pack-year history of smoking and, if no longer smoking, smoking cessation within 15 years; or a 20 pack-year history of smoking with one additional risk factor. The guidelines emphasize that screening should be done within the context of a multidisciplinary program to manage downstream testing. Most other guidelines groups are reviewing current screening recommendations in light of a mortality benefit for high-risk screening demonstrated in the 2011 National Lung Screening Trial, although screening cost-effectiveness is not yet determined. All patients who smoke should be strongly counselled to quit smoking as the most effective intervention to reduce the risk of lung cancer. (See "Screening for lung cancer", section on 'Recommendations for screening by expert groups'.)
Endobronchial ultrasound-guided transbronchial needle aspiration — Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) appears to be a reasonable substitute for mediastinoscopy in the appropriate clinical setting (ie, general anesthetic, rapid on-site cytology, different needles for each lymph node station). This was demonstrated by a prospective cohort study of 190 patients with potentially resectable lung cancer and small mediastinal lymph nodes that found no significant differences in the pathological lymph node stage when EBUS-TBNA was compared with mediastinoscopy [37]. The sensitivity, specificity, positive predictive value, and negative predictive value for EBUS-TBNA and mediastinoscopy were nearly identical for the two approaches. (See "Endobronchial ultrasound: Indications, advantages, and complications", section on 'Regional lymph nodes'.)
VASCULAR SURGERY
Supervised exercise therapy versus percutaneous intervention — Several studies have demonstrated the benefit of a supervised exercise rehabilitation program in reducing symptoms of claudication. A systematic review identified 11 trials performed between 1990 and 2011 comparing supervised exercise therapy with intervention, and found that a combination of percutaneous transluminal angioplasty (PTA) and exercise (supervised exercise therapy or exercise advice) may produce greater changes in walking distance compared with exercise or PTA alone, but the improvements did not uniformly translate to a quality of life improvement [38]. (See "Medical management of claudication", section on 'Supervised exercise therapy'.)
Clopidogrel hypersensitivity reactions — Hypersensitivity reactions develop in 1 to 4 percent of patients who receive clopidogrel following a coronary artery stenting procedure. Management options include stopping clopidogrel and changing to another antiplatelet agent, restarting the clopidogrel using a desensitization procedure, or continuing the drug while treating the patient with systemic glucocorticoids and antihistamines (ie, “treating through”). An observational study reported outcomes for a series of 62 patients with mild to moderate clopidogrel reactions who were managed by “treating through” and also evaluated with various allergy tests to define the nature of their reactions [39]. Hypersensitivity signs and symptoms included generalized macular rash, localized skin reaction, and isolated urticaria or angioedema. All patients received a 20-day course of prednisone, during which 95 percent had resolution of symptoms by a mean of 5 days. All patients were able to complete the minimum desired period of clopidogrel treatment (ie, 1 to 12 months). (See "Antithrombotic therapy for intracoronary stent implantation: General use", section on 'Hypersensitivity'.)
Prevention of portal vein thrombosis — Preliminary results are available from a prospective, randomized trial of enoxaparin for the prevention of portal vein thrombosis (PVT) in patients with cirrhosis [27]. During the one-year study period, PVT occurred significantly more often in those taking placebo (6 of 36, 17 percent) than in those taking enoxaparin (0 of 34). No hemorrhagic events were attributed to enoxaparin. Enoxaparin use was also associated with a significantly lower incidence of hepatic decompensation (53 versus 12 percent). (See "Coagulation abnormalities in patients with liver disease", section on 'Prevention'.)
Safety of dabigatran — Increasing concerns have been raised about the safety of the orally active direct thrombin inhibitor dabigatran:
These observations, as well as reports of deaths among trauma victims receiving dabigatran [41], have called into question the safety of this agent in trauma patients, older patients, and those with renal disease. (See "Anticoagulants other than heparin and warfarin", section on 'Bleeding and thrombotic events'.)
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.
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