Study reference

(first author, year of publication)

Bias due to a non-representative or ill-defined sample of patients?

(unlikely/likely/unclear)

Bias due to insufficiently long, or incomplete follow-up, or differences in follow-up between treatment groups?

(unlikely/likely/unclear)

Bias due to ill-defined or inadequately measured outcome ?

(unlikely/likely/unclear)

Bias due to inadequate adjustment for all important prognostic factors?

(unlikely/likely/unclear)

Newman, 2018

Likely - Patients without sleeve are ‘older’ perhaps less experienced surgeons? + Small control group (N=20) versus. the large case group (N=200).

“Patients with silicone and saline implants in periareolar breast augmentation. To be included in the study, patients had to be at least 1 year postoperative from the date of implantation. Patients who had been in for a follow-up, 3 or more years postoperatively were not contacted.

“Twenty patients having periareolar breast augmentations between July 1, 2008, and December 9, 2010, without a Keller funnel, but using conventional change in glove and tegaderm barrier no touch precautions, were followed to examine the baseline rate of capsular contracture for the practice.

Before 2014, any augmentations done with the use of a Keller funnel were done with the KF-1 type Keller funnel (73 of the augmentations included in this study). Upon its release in 2014, augmentations were done with the KF-2 type Keller funnel (93 of the augmentations included in this study)”.

Unlikely – The follow up was similar in both groups.

Due to the inclusion criteria, follow-up had to be at least one year. Patients who had been in follow-up 3 years or more were not contacted.

“In group A, those having augmentations without a Keller funnel (n = 20), there was a response/follow-up rate of 75%, leaving 15 patients included in the study results in group A (4 patients responded, but were not able to follow-up and were therefore excluded)”.

“In group B (n = 217), there was a response/follow-up rate of 70% leaving 151 patients included in the study results

for group B (17 patients responded, but were not able to follow-up and were therefore excluded)”.

“Any patient reporting they were unsure about whether or not they had any type of contracture was asked to come into the office for clinical examination. Any patient who was unsure and could not come in to the office to be evaluated was excluded

from the study (n = 21)”.

Unlikely – Blinding was not mentioned in the study. However, grade III or IV appear abnormal, and are clearly distinguishable between grade I or grade II judgements. Therefore, the outcome measure is objective, and will not result in detection bias.

Vrouwen rapporteren zelf de uitkomstmaat:

“Each patient included in the study was contacted by phone or e-mail and asked if they had had any complications

regarding their breast augmentation including hardening, unevenness, pain, general discomfort, reaugmentation,

and so on. Clinical records, photographs,

and postaugmentation visits were reviewed. Patients were asked to reply with images if possible and were also sent the article “Capsular contracture: what is it? What causes it? How can it be prevented and managed?”.15 Any patient reporting

they were unsure about whether or not they had any type of contracture was asked to come into the office for clinical examination”.

Unclear

Patient characteristics were not taken into account (BMI, roken). Therefore it is unclear whether the groups were comparable at baseline and whether it was required to adjust for potential confounders.

“To control for variations, the sole surgical practice affecting placement in either group was the use of a funnel. All surgeries were performed by the same surgeon, in the

same in-office operating suite, using the same antibiotic irrigation rinse (single antibiotic rinse of clindamycin or cefazolin

depending on allergies), skin prep with betadine, and distribution of implant manufacturer”.

Flugstad, 2016

Likely - Patients without sleeve are ‘older’ perhaps less experienced surgeons?

“Group 1 is a historical control group’.

In contrast to the study of Newman, the control group is of similar size compared to the experimental group with sleeve.

Unlikely – A one year study period after implant placement was chosen. The time period to evaluate if a reoperation due to capsular contracture occurred after primary surgery was identical for both groups

Unlikely – Blinding was not mentioned in the study. However, the primary outcome was development of Grade III or IV capsular contracture that led to reoperation. This is an objective outcome measure, and will therefore not result in detection bias.

Unclear - Demographic data was not collected, and therefore it remains unknown whether the groups were comparable at baseline and whether it is required to adjust for potential confounders.

Wiener, 2007

Likely - Patients from different dates were included, patients in the earlier groups have less experienced surgeons?

Unclear - the length of follow-up is not reported in the study.

Unlikely - Blinding was not mentioned in the study. However, the primary outcome was development of Grade II - IV capsular contracture that led to reoperation. This is an objective outcome measure, and will therefore not result in detection bias.

Unclear – No statement about comparability of the groups. Nothing is included about potential confounders and multivariate analyses were not performed.

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Newman, 2018

Type of study:

Observational study

Setting and country:

Retrospective

Funding and conflicts of interest:

The authors have no financial interest to declare

in relation to the content of this article. The Article Processing

Charge was paid for by the authors.

Inclusion criteria:

Patients with silicone and saline implants in periareolar breast augmentation. Patients who had been in for a follow-up, 3 or more years postoperatively were not

contacted. To be included in the study, patients had to be at least 1 year postoperative from the date of implantation.

Exclusion criteria:

To eliminate the number of confounding variables, patients

having any type of breast augmentation surgery after any radiation or chemotherapy were excluded from the study.

Any patient who was unsure and

could not come in to the office to be evaluated was excluded

from the study (n = 21).

N total at baseline:

Intervention: 217 patients with Keller funnel (2010-2017)

Control: 20 patients without Keller funnel (2008-2010)

Important prognostic factors²:

For example

age ± SD:

Not mentioned in the paper.

Groups comparable at baseline?

To control for variations, the sole surgical practice affecting

placement in either group was the use of a funnel.

All surgeries were performed by the same surgeon, in the

same in-office operating suite, using the same antibiotic irrigation

rinse (single antibiotic rinse of clindamycin or cefazolin

depending on allergies), skin prep with betadine,

and distribution of implant manufacturer.

Describe intervention (treatment/procedure/test):

Periareolar breast augmentations in which a Keller funnel was used for insertion (2011-2017)

Describe control (treatment/procedure/test):

Periareolar breast augmentation without a Keller funnel used for insertion (2008-2010).

Using conventional change in glove and tegaderm barrier no touch precautions.

Length of follow-up:

The average

postoperative follow-up time for patients in this study was

23 months.

Loss-to-follow-up:

Intervention (group B) = 217 with augmentation after 2010 with a funnel. They had a response rate of 70%, leaving 151 patients included in the study.

Reasons (describe): 17 responded, but were not able to follow-up and were therefore excluded.

Control (group A) = 20 patients without a Keller funnel. response/follow-up rate of 75% >> leaving 15 patients included in the study.

Reasons (describe): 4 responded but were not able to follow-up and therefore excluded).

Incomplete outcome data:

No incomplete outcome data, as patients were excluded:

“Any patient reporting

they were unsure about whether or not they had any

type of contracture was asked to come into the office for

clinical examination. Any patient who was unsure and could not come in to the office to be evaluated was excluded from the study (n = 21).”

Outcome measures and effect size (include 95%CI and p-value if available):

Rate of capsular contracture.

Control :

3 grade 3 or 4 capsular contractures (3/30 = 10%).

*15 patients and 30 breasts implants.

Intervention:

4 grade 3 or 4 capsular contractures (4/300=1.3%).

*151 patients and 300 implants.

There was a 87% reduction in the incidence or capsular contracture (p=0.0019).

PICO: sleeve.

All patients were skin prepped with betadine solution, and pockets were irrigated using a single antibiotic rinse (clindamycin with saline).

Conclusion: This study shows that the use of a Keller funnel intraoperatively can statistically significantly reduce the occurrence of capsular contraction in periareolar breast augmentations, which is a major concern in this technique.

Flugstad, 2016

Type of study:

Observational study.

Setting and country: Multicenter retrospective study.

Funding and conflicts of interest: Dr Pozner is on the Advisory Board for Allergan (Irvine, CA),

Canfield (Fairfield, NJ), Merge (Chicago, IL), Midmark (Dayton,

OH), New Beauty (Boca Raton, FL), and Valeant (Bridgewater,

NJ); a Speaker for Alma (Buffalo Grove, IL), Lifecell (Bridgewater,

NJ), Solta/Sound Surgical (Hayward, CA), and Zeltiq (Pleasanton,

CA); a Stockholder in Keller Medical (Stuart, FL), Revance

(Newark, CA), and TDM (Miami, FL); on the Advisory Board

and Stockholder for Cytrellis (Boston, MA) and RealSelf

(Seattle, WA); an Investigator for Cynosure/HOYA (Westford,

MA); a Board Member and Stockholder for the Plastic Surgery

Channel (Dallas, TX); an Investigator for and Stockholder in

Invasix (Irvine, CA); on the Clinical Advisory Panel for Mentor

(Santa Barbara, CA); on the Medical Advisory Board and Consultant

for Merz (Raleigh, NC); a Consultant for and Stockholder

in Sciton, Inc. (Palo Alto, CA); a Consultant and Speaker

for Ulthera (Mesa, AZ); on the Advisory Board and an Investigator

for Syneron (Irvine, CA); and a Speaker for and Stockholder in

Thermi (Irving, TX). Dr Baxter is a Consultant and Speaker for

Allergan (Irvine, CA). Dr Creasman is an Investor in Strathspey

Crown (Newport Beach, CA) and Alphaeon (Irvine, CA). Dr Messa

is a Shareholder in Strathspey Crown (Newport Beach, CA).

Dr Kortesis is a Consultant for Mentor (Santa Barbara, CA); an

Investigator for RXI (Marlborough, MA); and a Research Study

Coordinator and Participant for Cohera (Pittsburgh, PA), Mentor,

Sientra (Santa Barbara, CA), and RXI. Drs Flugstad, Egrari, Oliva,

Martin, and Schlesinger have nothing to disclose.

Keller Medical, Inc. (Stuart, Florida) is the manufacturer of the

Keller Funnel and provided funding for this project. No surgeons

were provided any direct compensation for their participation.

Keller Medical provided reimbursement to support staff

and/or to the clinical practice as compensation for the allocation

of staff resources associated with data collection. Keller

Medical also assisted with communication between the clinical

sites, provided editorial services, and provided compensation

to the bio-statistician. Each author states that there is no corporate

or financial conflict of interest related to Keller Medical or

with the collection of data in this study.

Inclusion criteria:

At nine participating private practice centers, we retrospectively

reviewed the surgical records from March 2006 to December 2012 for consecutive female patients undergoing

primary breast augmentation with silicone gel implants. The study

sites selected were well established practices that performed a

large volume of breast augmentation surgery, and had recently

adopted the use of the Keller Medical KF-1 insertion funnel

in virtually all of their primary augmentation cases.

Exclusion criteria: To minimize the number of technique-related factors introduced

by various surgeons, revisionary breast augmentation, breast

reconstruction, or breast augmentation, surgeries performed

in combination with secondary surgical procedures of the

breast (eg, mastopexy, fat injection) were excluded.

N total at baseline:

7 centers were included.

Intervention: 1620 surgeries (3240 implants)

Control: 1177 breast augmentations (2354 implants).

Important prognostic factors²:

Groups comparable at baseline?

Unknown – as demographic data was not collected.

“Demographic data such as age and BMI were not avail

Able from all sites. Since all sites were high volume centers in different regions of the United States, the study population was thought to closely represent the population of

breast augmentation patients as a whole”.

We acknowledge that there are many important variables

not directly analyzed in this protocol that may influence de

velopment

of capsular contracture including implant type texturing, incision placement, pocket placement, average

volume, aftercare such as bra use, variations between

centers, etc. There are all technique-related factors that have suggested effects on capsule rates. Comprehensive data collection and analysis were assumed to remain unchanged at each site after funnel adoption.

Describe intervention (treatment/procedure/test):

The experimental group, augmentations with the insertion funnel.

Describe control (treatment/procedure/test):

Historical control group, augmentation done without the insertion funnel.

Length of follow-up:

1 year.

The time period to

evaluate if a reoperation due to capsular contracture occurred after primary surgery was identical for both groups.

Loss-to-follow-up:

The true number of patients lost to follow-up is not known.

Incomplete outcome data:

Not reported.

Outcome measures and effect size (include 95%CI and p-value if available):

The primary outcome variable was development of Baker Grade III or IV capsular contracture that led to reoperation.

Capsulerelated

reoperations occurring within 12 months of implant

placement were included as events in each group (events counted per breast).

The rate of reoperation

due to capsular contracture was higher without use

of the insertion funnel (1.49%), compared to Group 2,

using the funnel (0.68%). The reduction in Grade III and IV

capsule detection was 54.4%. The difference between

Groups 1 and 2 was statistically significant at P=0.004 using Fisher’s exact test. Logistic regression analysis was used to examine the effects of treatment (funnel versus no funnel) and

study site (surgeon) on the incidence of reoperation.

By logistic regression, the odds ratio for reoperation

due to capsular contracture for Group 1 (no funnel)

was 2.31 (95% CI: 1.18-4.53) P=0.023.

Authors’ conclusion:

With insertion funnel use in primary breast augmentation, a significant reduction in the incidence of reoperations performed due to capsular contracture within 12 months of

primary breast augmentation was observed. Further study

is needed using the funnel while more precisely controlling for the many variables that contribute to capsular contracture.

A more traditional controlled, prospective study is needed; however, this study does provide encouraging preliminary

evidence to support the hypothesis that use of the

insertion funnel may significantly benefit breast augmentation

patients.

Note: 5/7 surgeons reported changes in implant handling technique related to incorporation of the insertion funnel.

Wiener, 2007

Type of study:

Review and comparison of the data used by the FDA.

Setting and country:

Retrospective cohort study.

Funding and conflicts of interest:

The author has no financial interest or association

in any product, device, or company mentioned in the

article.

Inclusion criteria:

A review of breast augmentations performed

from January of 1998 through September of 2005

showed four phases of Betadine use involving 1244

patients. Phase IV added

coverage of the nipple-areola complex and incision

with Betadine-soaked gauze. All augmentations were performed

for aesthetic reasons; there were no reconstructive

cases.

Exclusion criteria: not reported.

N total at baseline:

Intervention: 211 (group 4). (November 2004 – September 2005)

Control: 154 (group 3) > prior to the use of nipple shields. February 2004 – November 2004

Important prognostic factors²:

Groups comparable at baseline?

Not reported.

Describe intervention (treatment/procedure/test):

Betadine pocket irrigation with Betadine-soaked gauze coverage of the nipple areola complex.

Describe control (treatment/procedure/test):

Betadine pocket irrigation without Betadine-soaked gauze coverage of the nipple areola complex.

Length of follow-up:

Median follow-up 10 versus. 11 months.

Loss-to-follow-up:

Not reported.

Incomplete outcome data:

Not reported.

Outcome measures and effect size (include 95%CI and p-value if available):

Capsular contracture, for the purpose of this article, was defined as any clinically significant hardening of the breast, distortion due to con

tracture, or significant restriction of implant mo

tion in the breast pocket, as I used only round, smooth implants. This would correlate with grade 2 to grade 4 capsular contracture.

No. of contractures:

Group 3: 5 (3.2%)

Group 4: 1 (0.5%)

The study was not adjusted for any potential confounders.

Note: Powder-free gloves were used by the entire

operating team, and gloves were changed before

the implant was handled.

Note: betadine irrigation was used in this comparison.

Authors’ conclusion:

This article confirms other studies reporting that the use of betadine has no effect on the rate of deflation of a saline breast implant.

Note: the aim of the study was to assess the safety of the use of Betadine with regard to the number of inflations and capsular contracture.